2-(((4-Chlorophenyl)sulfonyl)methyl)-1,4-difluorobenzene → 3-[(4-Chlorophenyl)sulfonyl]-3-(2,5-difluorophenyl)-1-propanol

Participants

Reaction Conditions

Reaction Steps

Process 2: Under an argon atmosphere and at −78° C., n-butyl lithium (a 1.57M hexane solution, 4.62 ml, 7.26 mmol) was added to a dimethoxyethane solution (50 ml) of the 2-[(4-chlorophenyl)sulfonylmethyl]-1,4-difluorobenzene (2.00 g, 6.60 mmol) obtained in Example 5. The temperature of the resulting mixture was elevated to room temperature, and stirring was performed for 15 minutes. After cooling the reaction mixture to −78° C., a dimethoxyethane solution (5 ml) of t-butyl-(2-iodoethyloxy)dimethylsilane (2.08 g, 7.26 mmol) was added thereto. The resulting mixture was stirred at room temperature for 15 hours. Water was added to the reaction mixture, followed by extraction with ether. The extracts were combined, washed successively with water and brine, dried over magnesium sulfate and then, concentrated. The residue thus obtained was subjected to short silica gel chromatography (hexane:ethyl acetate=7:1) to remove high-polarity impurities. The resulting oil was dissolved in tetrahydrofuran (50 ml), and to the resulting solution was added tetrabutylammonium fluoride (a 1M tetrahydrofuran solution, 14.5 ml, 14.5 mmol). After stirring for 2 days, the solvent was distilled off. The residue thus obtained was dissolved in dichloromethane, followed by successive washing with 1N hydrochloric acid, water, and brine, driying over magnesium sulfate and concentration. The residue thus obtained was subjected to chromatography on a silica gel column, and the fraction obtained from the hexane:ethyl acetate=1:1 eluate was concentrated, whereby the title compound (2.07 g, 5.82 mmol, 88%) was obtained as a colorless solid.

Provenance & Evidence