Sodium ethoxide → 1-[4'-(4"-Chlorophenyl)phenyl]-3,3-dicarboethoxy-1-oxo-7-phenylheptane

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Reaction Steps

The general method of the preparation of 3-(4-methoxyphenyl)-1-iodopropane was used to prepare 4-methoxyphenethyl iodide, and 3-methoxyphenethyl iodide from 4-hydroxyphenethyl iodide and 3-hydroxyphenethyl iodide. ##STR181## Step 2 (D)--Preparation of 1-phenyl-3-bromo-1-propyne. Phosphorous tribromide (2.62 mL, 27.6 mmol) was added to a solution of 3-phenyl-2-propyn-1-ol (10.0 g, 76 mmol) and pyridine (0.14 mL, 1.77 mmol) in diethyl ether (22 mL) at a rate to maintain reflux. After addition, the mixture was heated at 40° C. for 2 h. The mixture was cooled and poured onto ice. The organic layer was separated and diluted with diethyl ether (100 mL), washed with saturated sodium bicarbonate (2×50 mL) and saturated sodium chloride (50 mL). The organic layer was dried (MgSO4), filtered and concentrated in vacuo to afford 1-phenyl-3-bromo-1-propyne (13.4 g, 90%). ##STR182## Step 2 (E)--Preparation of 2-(benzyloxy)bromoethane. A solution of triphenyl phosphine (2.1 g, 7.9 mmol) in dry methylene chloride (16 mL) was added dropwise over 10 min to a stirred mixture of N-bromosucccinimnide (1.4 g, 7.9 mmol) in dry methylene chloride (23 mL) at -78° C. The reaction was kept in the dark and stirring was continued until all the N-bromosucccinimide had dissolved (10 min). A solution of 2-(benzyloxy)ethanol in dry methylene chloride (10 mL) was added dropwise. The cooling bath was removed and stirring was continued for 12 h at rt. The organic layer was then concentrated in vacuo and passed through a silica plug with 1:1 hexane:methylene chloride to afford 2-benzyloxy)bromoethane (1.20 g, 85%). ##STR183## Step 3 Ethyl 2-carboethoxy-4[4'-(4"-chlorophenyl)phenyl]-4-oxobutanoate (0.40 g, 1.02 mmol) was added in one portion at rt to a solution of sodium ethoxide (0.08 g, 1.12 mmol) in DME (1 mL). After 15 min, 4-phenyl-1-iodobutane (0.24 g, 0.93 mmol) in DME (3 mL) was added. The resulting solution was stirred for 18 h. The solvent was concentrated in vacuo and the resulting oil dissolved in CH2Cl2 (100 mL) and washed with water (100 mL). The phases were separated and the aqueous phase was extracted with CH2Cl2 (2×50 mL). The combined organic phases were dried (MgSO4), filtered, and concentrated in vacuo. The resulting oil was purified by flash chromatography on silica gel using a gradient of ethyl acetate/hexane (10% to 25% ethyl acetate) as the eluent to afford a crystalline solid which was recrystallized with hexane and ethyl acetate to afford 1-[4'-(4"-chlorophenyl)phenyl]-3,3-dicarboethoxy-1-oxo-7-phenylheptane (0.272 g, 28%). MP 67-69° C.

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