Lithium Hexamethyldisilazide → HCID 57794765, compound

Participants

Reaction Conditions

Reaction Steps

To 765 mL toluene cooled to 0° C. was added 1.0 M LHMDS in hexanes (148.1 mL, 148.1 mmol, 1 eq). To this solution was added (1R)-3-cyano-3-phenyl-1-{[(phenylmethyl)oxy]methyl}propyl 4-methylbenzenesulfonate (43.0 g, 98.73 mmol, 1 eq), accessed via the method of Preparation 2, in 236 mL toluene. The reaction mixture was stirred at 0° C. for 16 h, then washed successively with water and brine, dried over MgSO4, filtered and concentrated to give a yellow oil that was shown to be an 8:2 diastereomeric mixture of the title compound to the product of Preparation 3A. The desired diastereomer (16.0 g, 62%) was separated by silica gel flash chromatography using 9:1→8:2 hexanes in ethyl acetate. 1H NMR (300 MHz, CDCl3) δ 7.44-7.15 (m, 10H), 4.28-4.19 (m, 2H), 3.31-3.27 (m, 1H), 2.94-2.84 (m, 1H), 2.22-2.15 (m,1H), 1.76-1.72 (m, 1H), 1.47-1.44 (m, 1H). ES-LCMS m/z 264.1 (M+H).

Provenance & Evidence