Cyclohexane, (bromomethyl)- → HCID 46221150, compound

Participants

Reaction Conditions

Reaction Steps

A solution of freshly prepared lithium diisopropylamide (16.3 mL of a 0.31 M stock solution, 5.04 mmol) cooled to −78° C. was treated with (3,4-dichloro-phenyl)-acetic acid methyl ester (1.0 g, 4.58 mmol) in tetrahydrofuran/hexamethylphosphoramide (8.6 mL, 3:1). The resulting solution was stirred at −78° C. for 45 min. At this time, the reaction was treated with a solution of bromomethylcyclohexane (1.92 mL, 13.76 mmol) in hexamethylphosphoramide (1 mL). The reaction mixture was stirred at −78° C. for 3 h. The reaction was warmed to 25° C. and stirred at 25° C. for 16 h. The reaction mixture was then quenched by the dropwise addition of a saturated aqueous ammonium chloride solution (20 mL). This mixture was poured into water (100 mL) and extracted with ethyl acetate (3×50 mL). The organics were dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 75/25 hexanes/ethyl acetate) afforded 3-cyclohexyl-2-(3,4-dichloro-phenyl)-propionic acid methyl ester (1.5 g, quant.) as a clear oil: EI-HRMS m/e calcd for C16H20Cl2O2 (M+) 314.0840, found 314.0836.

Provenance & Evidence