Lithium Hydroxide → HCID 69968459, compound

HRID 2289106Notes

Reaction equation

HRID 2289106 reaction equation
COC(=O)CC1C=CC(O)=C(Cl)C=1.C(=O)([O-])[O-].[K+].[K+].C1(CC2C3ON=C(C4C=CC=CC=4)C=3C=CC=2OCCCBr)CC1.C[CH:45]([C:49]1[CH:54]=[CH:53][C:52]([O:55][CH2:56][CH2:57][CH:58]([O:60][C:61]2[CH:62]=[CH:63][C:64]3[C:65]([C:74]4[CH:79]=[CH:78][CH:77]=[CH:76][CH:75]=4)=[N:66][O:67][C:68]=3[C:69]=2[CH2:70][CH:71]2[CH2:73][CH2:72]2)[CH3:59])=[C:51]([Cl:80])[CH:50]=1)[C:46]([OH:48])=[O:47].[OH-].[Li+]>CN(C=O)C.CO.O>[Cl:80][C:51]1[CH:50]=[C:49]([CH2:45][C:46]([OH:48])=[O:47])[CH:54]=[CH:53][C:52]=1[O:55][CH2:56][CH2:57][CH:58]([O:60][C:61]1[CH:62]=[CH:63][C:64]2[C:65]([C:74]3[CH:79]=[CH:78][CH:77]=[CH:76][CH:75]=3)=[N:66][O:67][C:68]=2[C:69]=1[CH2:70][CH:71]1[CH2:73][CH2:72]1)[CH3:59]

Participants

9

Reactant 5

HCID 3939Lithium HydroxideHCID 11430Potassium CarbonateHCID 92625Methyl 3-chloro-4-hydroxyphenylacetateHCID 69967358HCID 69967358, compoundHCID 69968717HCID 69968717, compound

Product 1

HCID 69968459HCID 69968459, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 7-cyclopropylmethyl-3-phenyl-6-hydroxybenz-[4,5]-isoxazole (0.25 grams) in 2-butanone (3.0 mL) was treated with 1,3-dibromopropane (0.48 mL) and potassium carbonate (0.50 grams). The mixture was refluxed for 4 hours. The reaction mixture was partitioned between isopropyl acetate and pH 4 buffer. The organic was washed once with water, then dried over magnesium sulfate. The organic was filtered and evaporated to an oil which was flitered through a silica gel plug using methylene chloride and hexane (1:2) to give 7-cyclopropylmethyl-3-phenyl-6-(3-bromopropyloxy)benz-[4,5]-isoxazole. A solution of 3-chloro-4-hydroxyphenylacetic acid methyl ester (42.0 mg) in DMF (1.0 mL) was treated with potassium carbonate (26 mg) and this mixture was stirred for 0.5 hours. Then 7-cyclopropylmethyl-3-phenyl-6-(3-bromopropyloxy)benz-[4,5]-isoxazole was added and the mixture was stirred over night. The reaction mixture was partitioned between ethyl acetate and 1 M HCl solution. The organic was dried over sodium sulfate and filtered. The solvent was removed in vacuo and the residue was chromatographed on silica gel using methlene chloride and hexane (1:1) to give an oil. A solution of methyl 3-chloro-4-(3-(3-phenyl-7-cyclopropylmethyl-6-benz-[4,5]-isoxazoloxy)-butyloxy)phenylacetic acid (0.04 grams) in methanol (1.5 mL) was treated with a solution of lithium hydroxide in water (1.01 M; 0.1 mL). The reaction was refluxed 1 hour. The reaction mixture was partitioned between isopropyl acetate and 0.1N HCl. The organic was dried over magnesium sulfate, filtered and concentrated to a solid. The solid was suspended in methylene chloride/cyclohexane (1:1; 2 mL). The mixture was refluxed briefly and cooled to 0° C. The title compound was isolated by filtration.

Workup

  1. stirringthe mixture was stirred over night
  2. customThe reaction mixture was partitioned between ethyl acetate and 1 M HCl solution
  3. dry with materialThe organic was dried over sodium sulfate
  4. filtrationfiltered
  5. customThe solvent was removed in vacuo
  6. customthe residue was chromatographed on silica gel
  7. customto give an oil
  8. temperatureThe reaction was refluxed 1 hour
  9. customThe reaction mixture was partitioned between isopropyl acetate and 0.1N HCl
  10. dry with materialThe organic was dried over magnesium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated to a solid
  13. temperatureThe mixture was refluxed briefly

Sources & evidence

ORD record
ord-6274d17735e641948de6750359886988
Source dataset
uspto-grants-2000_07
Patent number
US06090836

Reaction notes

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