Dimethyl Sulfoxide → HCID 86760286, compound

Participants

Reaction Conditions

Reaction Steps

A solution of 2.1 mL (24.2 mmol) of oxalyl chloride in 110 mL of CH2Cl2 at −78° C. was treated with 2.6 mL (36.8 mmol) of DMSO maintaining the temperature at less than −60° C. The resulting mixture was stirred cold for 5 min. A solution of 4.5 g (10.5 mmol) of 1-{[(3R,4S)-3-(hydroxymethyl)-4-(3-fluorophenyl)pyrrolidin-1-yl]methyl}cyclohexanecarboxylic acid, benzyl ester (from Step B) in 10 mL of CH2Cl2 was added maintaining the temperature at less than −60° C. The resulting mixture was stirred cold for 60 min. The mixture was treated with 15 mL (84.0 mmol) of N,N-diisopropylethylamine maintaining the temperature at less than −60° C. The reaction was warmed to 0° C., stirred for 20 min and quenched with 20 mL 0.5 N KHSO4. The mixture was partitioned between 250 mL of CH2Cl2 and 100 mL of H2O and the layers were separated. The aqueous layer was extracted with 250 mL of CH2Cl2. The combined organic phases were dried over MgSO4 and concentrated. Purification by Biotage Flash 40 using a 40 M cartridge and 1.0 L each of 95:5 to 90:10 v/v hexane/ethyl acetate as the eluant afforded the title compound: 1H NMR (500 MHz, CDCl3) δ 1.24–3.48 (18H), 5.16 (ABq, J=12.2, 2H), 6.90–7.02 (3H), 7.22–7.39 (6H), 9.59 (s, 1H).

Provenance & Evidence