Sodium Hydroxide → HCID 10022291, compound

A mixture of methyl (RS)-5-(3-benzyloxyphenyl)-5-oxo-4-phenylpentanoate (11.6 g),sodium hydroxide (60 mL; 1 N) and 1,4-dioxane is stirred at ambient temperature for 18 hours. The reaction mixture is then concentrated to dryness and dissolved in water (50 mL), acidified to pH 1 by treatment with concentrated hydrochloric acid, and extracted with chloroform. The organic layer is dried over magnesium sulphate, filtered and concentrated under reduced pressure to leave an oil. Trituration with a mixture of pentane and diethyl ether (1:1 v/v) and recrystallisation of the resulting solid with a mixture of diethyl ether and pentane gives (RS)-5-(3-benzyloxyphenyl)-5-oxo-4-phenylpentanoic acid (5.1 g), in the form of a white solid, m.p. 127-129° C. [Elemental analysis:-: C,76.9;H,5.94%; Calculated:- C,76.98;H,5.92%]. (ii) By proceeding in a similar manner but replacing the methyl (RS)-5-(3-benzyloxyphenyl)-5-oxo-4-phenylpentanoate by the appropriate quantity of methyl (RS)-5-(3-benzyloxyphenyl)-4-(2-chlorophenyl)-5-oxopentanoate and using 15% potassium hydroxide in methanol at reflux, there is prepared (RS)-5-(3-benzyloxyphenyl)-4-(2-chlorophenyl)-5-oxopentanoic acid in the form of a white solid after recrystallisation from ethyl acetate and pentane, m.p. 131-132° C. [Elemental analysis:- C,70.8;H,5.17;Cl,8.7%; Calculated; C,70.5;H,5.18;Cl,8.67%]. (iii) By proceeding in a similar manner but replacing the methyl (RS)-5-(3-benzyloxyphenyl)-5-oxo-4-phenylpentanoate by the appropriate quantity of methyl (RS)-5-(3-benzyloxyphenyl)-4-(2-methoxyphenyl)-5-oxopentanoate and using 15% potassium hydroxide in methanol at reflux for 1 hour, there is prepared (RS)-5-(3-benzyloxyphenyl)-4-(2-methoxyphenyl)-5-oxopentanoic acid in the form of a white solid after trituration with diisopropyl ether and pentane and recrystallisation from ethyl acetate, m.p. 143-144° C. [Elemental analysis:- C,74.3;H,6.10%. Calculated:- C,74.24;H,6.10%]. (iv) By proceeding in a similar manner but replacing the methyl (RS)-5-(3-benzyloxyphenyl)-5-oxo-4-phenylpentanoate by the appropriate quantity of methyl (RS)-5-(3-benzyloxyphenyl)-4-(2-methylphenyl)-5-oxopentanoate and using 15% potassium hydroxide in methanol at reflux for 1.5 hours, there is prepared (RS)-5-(3-benzyloxyphenyl)-4-(2-methylphenyl)-5-oxopentanoic acid in the form of a pale yellow solid after recrystallisation from a mixture of ethyl acetate and pentane, m.p. 121-122° C. [Elemental analysis:- C,77.3;H,6.28%. Calculated:- C,77.3; H,6.23%]. (v) By proceeding in a similar manner but replacing the methyl (RS)-5-(3-benzyloxyphenyl)-5-oxo-4-phenylpentanoate by the appropriate quantity of methyl (RS)-5-(3-benzyloxyphenyl)-4-(2-ethylphenyl)-5-oxopentanoate and using 15% potassium hydroxide in methanol at reflux for 2.5 hours, there is prepared (RS)-5-(3-benzyloxyphenyl)-4-(2-ethylphenyl)-5-oxopentanoic acid in the form of a white solid after recrystallisation from a mixture of ethyl acetate and pentane, m.p. 85-86° C. [Elemental analysis:- C,77.0;H,6.38%; Calculated:- C,77.58;H,6.51%]. (vi) By proceeding in a similar manner but replacing the methyl (RS)-5-(3-benzyloxyphenyl)-5-oxo-4-phenylpentanoate by the appropriate quantity of methyl (RS)-5-(3-benzyloxyphenyl)-4-(2-chloro-6-fluorophenyl)-5-oxopentanoate and using 15% potassium hydroxide in methanol at reflux for 1 hour, there is prepared (RS)-5-(3-benzyloxyphenyl)-4-(2-chloro-6-fluorophenyl)-5-oxopentanoic acid in the form of a white solid after trituration with diisopropyl ether/pentane and recrystallisation from ethyl acetate/pentane, m.p. 95-96° C. [Elemental analysis:- C,67.5; H,4.72;Cl,8.20%. Calculated:- C,67.53; H,4.72; Cl,8.31%]. (vii) By proceeding in a similar manner but replacing the methyl (RS)-5-(3-benzyloxyphenyl)-5-oxo-4-phenyl-pentanoate by the appropriate quantity of methyl (RS)-5-(3-benzyloxyphenyl)-4-(2,6-dichlorophenyl)-5-oxopentanoate and using 15% potassium hydroxide in methanol at reflux for 30 minutes, there is prepared (RS)-5-(3-benzyloxyphenyl)-4-(2,6-dichlorophenyl)-5-oxopentanoic acid in the form of a white solid after trituration with a mixture of diisopropyl ether and pentane and recrystallisation from a mixture of ethyl acetate and pentane, m.p. 113-114° C. [Elemental analysis:- C,64.6;H,4.43; Cl,15.70%. Calculated:- C,65.02;H,4.55; Cl,15.99%]. (viii) By proceeding in a similar manner but replacing the methyl (RS)-5-(3-benzyloxyphenyl)-5-oxo-4-phenylpentanoate by the appropriate quantity of methyl (RS)-5-(3-benzyloxyphenyl)-4-(4-methoxyphenyl)-5-oxopentanoate and using 15% potassium hydroxide in methanol at reflux for 1.5 hours, there is prepared (RS)-5-(3-benzyloxyphenyl)-4-(4-methoxyphenyl)-5-oxopentanoic acid in the form of a white solid after trituration with pentane, m.p. 74° C. [Elemental analysis:- C 74.3;H 5.95%. Calculated:- C 74.24; H,5.98%]. (ix) By proceeding in a similar manner but replacing the methyl (RS)-5-(3-benzyloxyphenyl)-5-oxo-4-phenylpentanoate by the appropriate quantity of methyl (RS)-5-(3-benzyloxyphenyl)-4-(3,4-dichlorophenyl)-5-oxopentanoate and using 15% potassium hydroxide in methanol at reflux for 3 hours, there is prepared (RS)-5-(3-benzyloxyphenyl)-4-(3,4-dichlorophenyl)-5-oxopentanoic acid in the form of a yellow solid after trituration from pentane, m.p. 87-88° C. [Elemental analysis:- C,64.50;H,4.51;Cl,15.60%. Calculated:- C,65.02;H,4.55;Cl,15.99%]. (x) By proceeding in a similar manner but replacing the methyl (RS)-5-(3-benzyloxyphenyl)-5-oxo-4-phenylpentanoate by the appropriate quantity of methyl (RS)-5-(3-benzyloxyphenyl)-4-(4-chlorophenyl)-5-oxopentanoate and using 15% potassium hydroxide in methanol at reflux for 1 hour, there is prepared (RS)-5-(3-benzyloxyphenyl)-4-(4-chlorophenyl)-5-oxopentanoic acid in the form of a white solid after chromatography on silica gel using a mixture of ethyl acetate and pentane (1:1 v/v) and trituration of the resulting solid with diisopropyl ether, m.p. 91° C. [Elemental analysis:- C,70.4;H,5.14; Cl,8.6%. Calculated:- C,75.5;H,5.17;Cl,8.67%]. (xi) By proceeding in a similar manner but replacing the methyl (RS)-5-(3-benzyloxyphenyl)-5-oxo-4-phenylpentanoate by the appropriate quantity of methyl (RS)-5-(3-benzyloxyphenyl)-4-(4-methylphenyl)-5-oxopentanoate and using 15% potassium hydroxide in methanol at reflux for 3.5 hours, there is prepared (RS)-5-(3-benzyloxyphenyl)-4-(4-methylphenyl)-5-oxopentanoic acid in the form of a white solid after recrystallisation from a mixture of diisopropyl ether and pentane, m.p. 105-106° C. [Elemental analysis:- C,77.1;H,6.17%. Calculated:- C,77.3;H,6.23%]. (xii) By proceeding in a similar manner but replacing the methyl (RS)-5-(3-benzyloxyphenyl)-5-oxo-4-phenylpentanoate by the appropriate quantity of methyl (RS)-5-(3-benzyloxyphenyl)-4-(3-chlorophenyl)-5-oxopentanoate and using 15% potassium hydroxide in methanol at reflux for 1.5 hours, there is prepared (RS)-5-(3-benzyloxyphenyl)-4-(3-chlorophenyl)-5-oxopentanoic acid in the form of a white solid after trituration with a mixture of diethyl ether and pentane and recrystallisation from a mixture of ethyl acetate and pentane, m.p. 110-111° C. [Elemental analysis:- C,70.3;H,5.10;Cl,8.50%. Calculated:- C,70.5;H,5.18;Cl,8.67%]. (xiii) By proceeding in a similar manner but replacing the methyl (RS)-5-(3-benzyloxyphenyl)-5-oxo-4-phenylpentanoate by the appropriate quantity of methyl (RS)-5-(3-benzyloxyphenyl)-4-(3-methoxyphenyl)-5-oxopentanoate and using 15% potassium hydroxide in methanol at reflux for 1 hour, there is prepared (RS)-5-(3-benzyloxyphenyl)-4-(3-methoxyphenyl)-5-oxopentanoic acid in the form of a white solid after trituration with a mixture of diisopropyl ether and pentane and recrystallisation from a mixture of ethyl acetate and pentane, m.p. 94-95° C. [Elemental analysis:- C,73.0;H,5.93%; Calculated for C25H24O5.0.25AcOEt:- C,73.22; H,6.14%]. (xiv) By proceeding in a similar manner but replacing the methyl (RS)-5-(3-benzyloxyphenyl)-5-oxo-4-phenylpentanoate by the appropriate quantity of methyl (RS)-5-(4-benzyloxyphenyl)-5-oxo-4-phenylpentanoate, there is prepared (RS)-5-(4-benzyloxyphenyl)-5-oxo-4-phenylpentanoic acid in the form of a white solid after trituration with pentane, m.p. 147-149° C. [Elemental analysis:- C,77.4;H,6.06%. Calculated:- C,76.98; H,5.92%]. (xv) By proceeding in a similar manner but replacing the methyl (RS)-5-(3-benzyloxyphenyl)-5-oxo-4-phenylpentanoate by the appropriate quantity of methyl (RS)-4-(3-benzyloxyphenyl)-4-oxo-3-phenylbutanoate, there is prepared (RS)-4-(3-benzyloxyphenyl)-4-oxo-3-phenylbutanoic acid in the form of a white solid after recrystallisation from a mixture of ethyl acetate and pentane, m.p. 150-152° C. [Elemental analysis:- C,76.7;H,5.67%. Calculated:- C,76.65; H,5.59%]. (xvi) By proceeding in a similar manner but replacing the methyl (RS)-5-(3-benzyloxyphenyl)-5-oxo-4-phenylpentanoate by the appropriate quantity of ethyl (RS)-6-(3-benzyloxyphenyl)-6-oxo-5-phenylhexanoate, there is prepared (RS)-6-(3-benzyloxyphenyl)-6-oxo-5-phenylhexanoic acid in the form of a white solid after trituration with pentane and recrystallisation from a mixture of ethyl acetate and cyclohexane, m.p. 107-109° C. [Elemental analysis:- C,77.0;H,6.22%. Calculated:- C,77.3;H,6.23%]. (xvii) By proceeding in a similar manner but replacing the methyl (RS)-5-(3-benzyloxyphenyl)-5-oxo-4-phenylpentanoate by ethyl (RS)-7-(3-benzyloxyphenyl)-7-oxo-6-phenylheptanoate, there is prepared (RS)-7-(3-benzyloxyphenyl)-7-oxo-6-phenylheptanoic acid in the form of an orange oil after chromatography on silica gel eluting with a mixture of pentane and ethyl acetate (8:1 v/v). [Elemental analysis:- C,77.2:H,66%; Calculated:- C,77.59; H,6.51%]. (xviii) By proceeding in a similar manner but replacing the methyl (RS)-5-(3-benzyloxyphenyl)-5-oxo-4-phenylpentanoate by the appropriate quantity of ethyl (RS)-6-(3-benzyloxyphenyl)-6-oxo-5-phenylhex-2-enoate, there is prepared (RS)-6-(3-benzyloxyphenyl)-6-oxo-5-phenylhex-2-enoic acid in the form of an oil after chromatography on silica gel eluting with a mixture of pentane and ethyl acetate (1:4 v/v). [Elemental analysis:- C,75.6;H,5.87%. Calculated:- C,75.96;H,5.73%]. (xix) By proceeding in a similar manner but replacing the methyl (RS)-5-(3-benzyloxyphenyl)-5-oxo-4-phenylpentanoate by the appropriate quantity of methyl (RS)-5-(3-benzyloxyphenyl)-5-oxo-4-(2-pyridyl)pentanoate and acidifying to pH 4.5 rather than pH 1 prior to extraction, there is prepared (RS)-5-(3-benzyloxyphenyl)-5-oxo-4-(2-pyridyl)pentanoic acid in the form of a white solid after chromatography on silica gel eluting with a mixture of pentane and ethyl acetate (1:1 v/v) followed by trituration with pentane, m.p. 99-104° C. [Elemental analysis:- C,73.2;H,5.91; N,3.5%. Calculated:- C,73.58;H,5.64;N,3.73%]. (xx) By proceeding in a similar manner but replacing the methyl (RS)-5-(3-benzyloxyphenyl)-5-oxo-4-phenylpentanoate by the appropriate quantity of methyl (3RS,4RS)-5-(3-benzyloxyphenyl)-3-methyl-5-oxo-4-phenylpentanoate, there is prepared (3RS,4RS)-5-(3-benzyloxyphenyl)-3-methyl-5-oxo-4-phenylpentanoic acid in the form of a white solid after trituration with pentane, m.p. 68-70° C. [Elemental analysis:- C,77.0; H,6.28%. Calculated:- C,77.29;H,6.22%]. (xxi) By proceeding in a similar manner but replacing the methyl (RS)-5-(3-benzyloxyphenyl)l-5-oxo-4-phenylpentanoate by methyl (2RS,4RS)-5-(3-benzyloxyphenyl)-2-methyl-5-oxo-4-phenylpentanoate, there is prepared (2RS,4RS)-5-(3-benzyloxyphenyl)-2-methyl-5-oxo-4-phenylpentanoic acid in the form of a white solid after recrystallisation from a mixture of ethyl acetate and pentane, m.p. 98-100° C. [Elemental analysis:- C,77.0;H,6.13%. Calculated:- C,77.29; H,6.22%]. (xxii) By proceeding in a similar manner, but replacing the methyl (RS)-5-(3-benzyloxyphenyl)-5-oxo-4-phenylpentanoate by the appropriate quantity of methyl (RS)-5-(3-methoxyphenyl)-4-(2-methylphenyl)-5-oxopentanoate, and carrying out the reaction at 60° C. for 3 hours, there is prepared (RS)-5-(3-methoxyphenyl)-4-(2-methylphenyl)-5-oxopentanoic acid, in the form of a white solid, m.p. 108-11 0° C. [Elemental analysis:- C,72.7; H,6.42%; Calculated:- C,73.1;H,6.45%]. (xxiii) By proceeding in a similar manner but replacing the methyl (RS)-5-(3-benzyloxyphenyl)-5-oxo-4-phenylpentanoate by the appropriate quantity of methyl (RS)-5-[3-(2-methoxybenzyloxy)phenyl]-5-oxo-4-phenylpentanoate, there is prepared (RS)-5-[3-(2-methoxybenzyloxy)phenyl]-5-oxo-4-phenylpentanoic acid in the form of a white solid after trituration with a mixture of pentane, ethyl acetate and acetic acid (72/28/1) and trituration with pentane, m.p. 111-113° C. [NMR(CDCl3):- 2.1-2.5(4H,m),3.9(3H,s), 4.6(1H,t),5.1(2H,s),6.9-7.6(13H)]. (xxiv) By proceeding in a similar manner but replacing the methyl (RS)-5-(3-benzyloxyphenyl)-5-oxo-4-phenylpentanoate by the appropriate quantity of methyl (RS)-5-[3-(3,4-methylenedioxybenzyloxy)phenyl]-5-oxo-4-phenylpentanoate, there is prepared (RS)-5-[3-(3,4-methylenedioxybenzyloxy)phenyl]-5-oxo-4-phenylpentanoic acid, m.p. 92-94° C. [Elemental analysis:- C,71.4;H,5.46%. Calculated:- C,71.8;H,5.29%]. (xxv) By proceeding in a similar manner, but replacing the methyl (RS)-5-(3-benzyloxyphenyl)-5-oxo-4-phenylpentanoate by the appropriate quantity of methyl (RS)-4-(2-methylphenyl)-5-[3-(2-methylpropoxy)phenyl]-5-oxopentanoate, and carrying out the reaction for 18 hours, there is prepared (RS)-4-(2-methylphenyl)-5-[3-(2-methylpropoxy)phenyl]-5-oxopentanoic acid, in the form of a white solid after recrystallisation from a mixture of ethyl acetate and hexane, m.p. 96-98° C. [Elemental analysis:- C,74.0;H,7.3%; Calculated:- C,74.5;H,7.39%]. (xxvi) By proceeding in a similar manner but replacing the methyl (RS)-5-(3-benzyloxyphenyl)-5-oxo-4-phenylpentanoate by the appropriate quantity of methyl (RS)-5-[3-(4-chlorobenzyl-oxy)phenyl]-4-(2-methylphenyl)-5-oxopentanoate, there is prepared (RS)-5-[3-(4-chlorobenzyl-oxy)phenyl]-4-(2-methylphenyl)-5-oxopentanoic acid, m.p. 131-133° C. [Elemental analysis; C,71.2;H,5.48%. Calculated:- C,71.0;H,5.48%]. (xxvii) By proceeding in a similar manner but replacing the methyl (RS)-5-(3-benzyloxyphenyl)-5-oxo-4-phenylpentanoate by the appropriate quantity of methyl (RS)-5-(3-cyclopentylmethoxyphenyl)-4-(2-methylphenyl)-5-oxopentanoate, there is prepared (RS)-5-(3-cyclopentylmethoxyphenyl)-4-(2-methylphenyl)-5-oxopentanoic acid, m.p. 104-105° C. [Elemental analysis:- C,75.7;H,7.60%. Calculated:- C,75.8; H,7.42%]. (xxviii) By proceeding in a similar manner but replacing the methyl (RS)-5-(3-benzyloxyphenyl)-5-oxo-4-phenylpentanoate by the appropriate quantity of methyl (RS)-5-[3-(3-thienylmethoxy)- phenyl]-4-(2-methylphenyl)-5-oxopentanoate, there is prepared (RS)-5-[3-(3-thienylmethoxy)phenyl]-4-(2-methylphenyl)-5-oxopentanoic acid hydrate, m.p. 94-98° C. [Elemental analysis:- C,67.1;H,5.60%. Calculated for C23H22O4S.H2O:- C,67.1; H,5.85%]. (xxix) By proceeding in a similar manner but replacing the methyl (RS)-5-(3-benzyloxy-phenyl)-5-oxo-4-phenylpentanoate by the appropriate quantity of methyl (RS)-5-[3-(2-fluorobenzyl-oxy) phenyl]-4-(2-methylphenyl)-5-oxopentanoate, there is prepared (RS)-5-[3-(2-fluorobenzyl-oxy)phenyl]-4-(2-methylphenyl)-5-oxopentanoic acid, m.p. 108-110C. [Elemental analysis:- C, 73.5;H,5.65%. Calculated:- C,73.9;H,5.70%]. (xxx) By proceeding in a similar manner but replacing the methyl (RS)-5-(3-benzyloxyphenyl)-5-oxo-4-phenylpentanoate by the appropriate quantity of methyl (RS)-5-[3-(2-furylmethoxy)phenyl]-4-(2-methylphenyl)-5-oxopentanoate, there is prepared (RS)-5-[3-(2-furylmethoxy)phenyl]-4-(2-methylphenyl)-5-oxopentanoic acid, m.p. 92-94° C. [Elemental analysis:- C,72.9;H,5.81%. Calculated:- C,73.0;H,5.86%]. (xxxi) By proceeding in a similar manner but replacing the methyl (RS)-5-(3-benzyloxyphenyl)-5-oxo-4-phenylpentanoate by the appropriate quantity of methyl (RS)-5-[3-(3-furylmethoxy)phenyl]-4-(2-methylphenyl)-5-oxopentanoate, there is prepared (RS)-5-[3-(3-furylmethoxy)phenyl]-4-(2-methylphenyl)-5-oxopentanoic acid, m.p. 83-85° C. [Elemental analysis:- C,72.6;H,5.66%. Calculated:- C,73.0; H,5.86%]. (xxxii) By proceeding in a similar manner but replacing the methyl (RS)-5-(3-benzyloxyphenyl)-5-oxo-4-phenylpentanoate by the appropriate quantity of methyl (RS)-5-[3-(3-chlorobenzyl-oxy)phenyl]-4-(2-methylphenyl)-5-oxopentanoate, there is prepared (RS)-5-[3-(3-chlorobenzyl-oxy)phenyl]-4-(2-methylphenyl)-5-oxopentanoic acid, m.p. 103-105° C. [Elemental analysis:- C,71.1;H,5.45%. Calculated:- C,71;H,5.48%]. (xxxiii) By proceeding in a similar manner but replacing the methyl (RS)-5-(3-benzyloxyphenyl)-5-oxo-4-phenylpentanoate by the appropriate quantity of methyl (RS)-5-[3-(4-methoxy-benzyloxy)phenyl]-4-(2-methylphenyl)-5-oxopentanoate, there is prepared (RS)-5-[3-(4-methoxybenzyloxy)phenyl]-4-(2-methylphenyl)-5-oxopentanoic acid, m.p. 132-133° C. [Elemental analysis; C,74.4;H,6.25%. Calculated:- C,74.4;H,6.25%]. (xxxiv) By proceeding in a similar manner but replacing the methyl (RS)-5-(3-benzyloxyphenyl)-5-oxo-4-phenylpentanoate by the appropriate quantity of methyl (RS)-4-(2-methylphenyl)-5-oxo-5-(3-(2-pyridylmethoxy)phenyl)pentanoate, there is prepared (RS)-4-(2-methylphenyl)-5-oxo-5-(3-(2-pyridylmethoxy)phenyl)pentanoic acid, m.p. 152-154° C. [Elemental analysis:- C,74.0;H,5.95%. Calculated:- C,74.0;H,5.95%]. (xxxv) By proceeding in a similar manner but replacing the methyl (RS)-5-(3-benzyloxyphenyl)-5-oxo-4-phenylpentanoate by the appropriate quantity of methyl (RS)-4-(2-methylphenyl)-5-oxo-5-[3-(2-thienylmethoxy)phenyl]pentanoate, there is prepared (RS)-4-(2-methylphenyl)-5-oxo-5-[3-(2-thienylmethoxy)phenyl]-pentanoic acid, m.p. 96-98° C. [Elemental analysis:- C,70.1; H,5.67%. Calculated:- C,70.0;H,5.62%]. (xxxvi) By proceeding in a similar manner, but replacing the methyl (RS)-5-(3-benzyloxyphenyl)-5-oxo-4-phenylpentanoate by the appropriate quantity of methyl (RS)-5-(2-methyl-3-benzyloxyphenyl)-4-(2-methylphenyl)-5-oxopentanoate, and carrying out the reaction for 18 hours, there is prepared (RS)-5-(2-methyl-3-benzyloxyphenyl)-4-(2-methylphenyl)-5-oxopentanoic acid, in the form of a white solid after recrystallisation from ethyl acetate, m.p. 177-178° C. [Elemental analysis:- C,77.7; H,6.54%; Calculated:- C,77.6;H,6.51%]. (xxxvii) By proceeding in a similar manner, but replacing the methyl (RS)-5-(3-benzyloxyphenyl)-5-oxo-4-phenylpentanoate by the appropriate quantity of methyl (RS)-5-(3,5-dibenzyloxyphenyl)-4-(2-methylphenyl)-5-oxopentanoate, and using a solution of potassium hydroxide in methanol (15% w/v) at reflux for 1.5 hours, and subjecting to flash chromatography on silica gel, eluting with a mixture of ethyl acetate and pentane (2:3 v/v), there is prepared (RS)-5-(3,5-dibenzyloxyphenyl)-4-(2-methylphenyl)-5-oxo-pentanoic acid, in the form of a pale yellow oil. [Elemental analysis:- C,76.6;H,6.08%; Calculated for C32H30O5.0.25AcOEt:- C,76.7;H,6.24%]. (xxxviii) By proceeding in a similar manner but replacing the methyl (RS)-5-(3-benzyloxyphenyl)-5-oxo-4-phenylpentanoate by the appropriate quantity of methyl (RS)-5-[3-(3-methoxybenzyloxy)phenyl]-4-(2-methylphenyl)-5-oxopentanoate, there is prepared (RS)-5-[3-(3-methoxybenzyloxy)phenyl]-4-(2-methylphenyl)-5-oxopentanoic acid, m.p. 72-74° C. [Elemental analysis:- C,74.6;H,6.27%. Calculated:- C,74.6; H,6.26%]. (xxxix) By proceeding in a similar manner but replacing the methyl (RS)-5-(3-benzyloxyphenyl)-5-oxo-4-phenylpentanoate by the appropriate quantity of methyl (RS)-5-[3-(3-aminobenzyloxy)-phenyl]-4-(2-methylphenyl)-5-oxopentanoate, there is prepared (RS)-5-[3-(3-aminobenzyloxy)phenyl]-4-(2-methylphenyl)-5-oxopentanoic acid in the form of an oil. [Elemental analysis:- C,73.9; H,6.34;N,3.43%. Calculated:- C,74.4;H,6.24; N,3.47%]. (xxxx) By proceeding in a similar manner but replacing the methyl (RS)-5-(3-benzyloxyphenyl)-5-oxo-4-phenylpentanoate by the appropriate quantity of methyl (RS)-5-[3-(3-isothiazolylmethoxy)phenyl]-4-(2-methylphenyl)-5-oxopentanoate, there is prepared (RS)-5-[3-(3-isothiazolylmethoxy)phenyl]-4-(2-methylphenyl)-5-oxopentanoic acid, m.p. 102-104° C. [Elemental analysis:- C,66.8;H,5.33;N,3.44%. Calculated:- C,66.8;H,5.35; N,3.54%]. (xxxxi) By proceeding in a similar manner, but replacing the methyl (RS)-5-(3-benzyloxyphenyl)-5-oxo-4-phenylpentanoate by the appropriate quantity of methyl (RS)-5-(3-benzyloxy-5-hydroxyphenyl)-4-(2,3-dimethylphenyl)-5-oxopentanoate, there is prepared (RS)-5-(3-benzyloxy-5-hydroxyphenyl)-4-(2,3-dimethylphenyl)-5-oxopentanoic acid. (xxxxii) By proceeding in a similar manner, but replacing the methyl (RS)-5-(3-benzyloxyphenyl)-5-oxo-4-phenylpentanoate by the appropriate quantity of methyl (RS)-5-(3-benzyloxy-4-methylphenyl)-4-(2-methylphenyl)-5-oxopentanoate, and using a solution of potassium hydroxide in methanol (15% w/v) at reflux for 1 hour, there is prepared (RS)-5-(3-benzyloxy-4-methyl-phenyl)-4-(2-methylphenyl)-5-oxopentanoic acid, in the form of a white solid after trituration with pentane, m.p. 94-98° C. [Elemental analysis:- C,77.1; H,6.58%. Calculated:- C,77.6;H,6.51%]. (xxxxiii) By proceeding in a similar manner but replacing the methyl (RS)-5-(3-benzyloxyphenyl)-5-oxo-4-phenylpentanoate by the appropriate quantity of methyl (RS)-4-(2-methylphenyl)-5-oxo-5-[3-(4-pyridy)methoxy)phenyl]pentanoate, there is prepared (RS)-4-(2-methylphenyl)-5-oxo-5-[3-(4-pyridylmethoxy)phenyl]pentanoic acid, m.p. 124-125° C. [Elemental analysis:- C,74.0;H,6.05;N,3.43%. Calculated:- C,74.0;H,5.95; N,3.60%]. (xxxxiv) By proceeding in a similar manner but replacing the methyl (RS)-5-(3-benzyloxyphenyl)-5-oxo-4-phenylpentanoate by the appropriate quantity of methyl (RS)-4-(2-methylphenyl)-5-[3-(3-methyl-2-thienylmethoxy)phenyl]-5-oxopentanoate, there is prepared (RS)-4-(2-methyl-phenyl)-5-[3-(3-methyl-2-thienylmethoxy)phenyl]-5-oxopentanoic acid, m.p. 88-90° C. [Elemental analysis:- C,70.3;H,5.98%; C24H24O4S requires C,70.6; H,5.92%]. (xxxxv) By proceeding in a similar manner but replacing the methyl (RS)-5-(3-benzyloxyphenyl)-5-oxo-4-phenylpentanoate by the appropriate quantity of methyl (RS)-4-(2-methylphenyl)-5-oxo-5-[3-(3-pyridylmethoxy) phenyl]pentanoate, there is prepared (RS)-4-(2-methylphenyl)-5-oxo-5-[3-(3-pyridylmethoxy)phenyl]pentanoic acid hydrate in the form of an oil. [Elemental analysis:- C,72.9;H,6.44; N,3.27%; Calculated for C24H23NO4.0.3H2O:- C,72.9;H,6.03;N,3.54%]. (xxxxvi) By proceeding in a similar manner, but replacing the methyl (RS)-5-(3-benzyloxyphenyl)-5-oxo-4-phenylpentanoate by the appropriate quantity of methyl (RS)-5-(3-benzyloxyphenyl)-4-(2,5-dimethylphenyl)-5-oxopentanoate, and using a solution of potassium hydroxide in methanol (15% w/v) at reflux for 0.75 hours, there is prepared (RS)-5-(3-benzyloxyphenyl)-4-(2,5-dimethylphenyl)-5-oxopentanoic acid, in the form of a white solid after trituration with diisopropyl ether, m.p. 146-148° C. [Elemental analysis:- C,77.2;H,6.5%. Calculated:- C,77.6;H,6.51%]. (xxxxvii) By proceeding in a similar manner, but replacing the methyl (RS)-5-(3-benzyloxyphenyl)-5-oxo-4-phenylpentanoate by the appropriate quantity of methyl (RS)-5-(3-benzyloxy-6-hydroxyphenyl)-4-(2-methylphenyl)-5-oxopentanoate, there is prepared (RS)-5-(3-benzyloxy-6-hydroxyphenyl)-4-(2-methylphenyl)-5-oxopentanoic acid, in the form of a yellow oil.

1. concentrationThe reaction mixture is then concentrated to dryness
2. dissolutiondissolved in water (50 mL)
3. extractionextracted with chloroform
4. dry with materialThe organic layer is dried over magnesium sulphate
5. filtrationfiltered
6. concentrationconcentrated under reduced pressure
7. customto leave an oil

ORD record

ord-38a3eae2c4324e9db7eecec7df0c2f96

Source dataset

uspto-grants-2001_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06211234B1