4-(5-Fluoro-2-methoxyphenyl)-2-methoxymethoxy-4-methyl-2-trifluoromethylpentanal → 1-(3,5-Dimethylphenyl)-5-(5-fluoro-2-methoxyphenyl)-3-methoxymethoxy-5-methyl-3-trifluoromethylhexan-2-ol

Participants

Reaction Steps

To a solution of 398 mg (1.1 mmol) of the above 4-(5-fluoro-2-methoxyphenyl)-2-methoxymethoxy-4-methyl-2-trifluoromethylpentanal in 4 mL of anhydrous THF, 10 mL (2.5 mmol) of a 0.25 M solution of 3,5-dimethylbenzylmagnesium bromide in THF was added. The mixture stirred for 4 hours and was then quenched with 10 mL of saturated ammonium chloride and extracted with three 10 mL portions of EtOAc. The combined organic layers were washed with three 5 mL portions of brine, dried over magnesium sulfate, filtered, and concentrated in vacuo. The mixture of diastereomers was purified by chromatography on silica gel eluting with dichloromethane-hexanes (0:100, then 10:90, then 15:85, then 20:80, then 25:75, then 3:7, then 4:6) to afford first 121 mg (22%) of a single diastereomer of 1-(3,5-dimethylphenyl)-5-(5-fluoro-2-methoxyphenyl)-3-methoxymethoxy-5-methyl-3-trifluoromethylhexan-2-ol, and then 137 mg (25%) of the second diastereomer.

Provenance & Evidence