Diisopropylamine → HCID 67099268, compound

Participants

Reaction Conditions

Reaction Steps

A 2.1 M solution of n-BuLi (11 mL, 23 mmol) in hexanes was added slowly to a 0° C. solution of diisopropylamine (4.0 mL, 28 mmol) in THF (10 mL). Stirring was continued at this temperature for an additional 10 min prior to cooling to −78° C. A solution of ethyl [4-(methylthio)phenyl]acetate (4.64 g, 18.9 mmol) in THF (15 mL) was then introduced and the mixture was stirred at −78° C. for 10 min, −40° C. for 10 min and finally at 0° C. for 5 min. The solution was recooled to −78° C. and a solution of (1R,2R)-2-[(benzyloxy)methyl]-4,4-difluorocyclohexanecarbaldehyde (4.64 g, 18.9 mmol) in THF (15 mL) was added down the flask wall over 5 min. Stirring was continued at −78° C. for 30 min then at −40° C. for 1 h. A saturated aqueous solution of NH4Cl was added and the reaction mixture was warmed to rt and partitioned between ethyl acetate and water. The organic phase was washed with saturated aqueous NaCl solution and dried over Na2SO4. Concentration in vacuo and flash chromatography on silica gel eluting with 3/7 ethyl acetate/hexanes gave ethyl 3-{2-[(benzyloxy)methyl]-4,4-difluorocyclohexyl}-3-hydroxy-2-[4-(methylthio)phenyl]propanoate as a faint-yellow, thick syrup. 1H NMR (400 MHz, d6-acetone) δ 7.43-7.33 (5H, m), 7.33-7.29 (2H, m), 7.15-7.11 (2H, m), 4.66 (1H, m), 4.57-4.49 (2H, m), 4.16-4.00 (2H, m), 3.74 (2H, d, J= 10.7 Hz), 3.45 (1H, dd, J=2.8, 9.5 Hz), 2.46 (3H, s), 1.84-1.75 (2H, m) 13.5 Hz), 1.73-1.63 (1H, m), 1.17 (3H, t, 7= 7.1 Hz).

Provenance & Evidence