Acetyl chloride → HCID 66700205, compound

Participants

Reaction Steps

To a solution of 1,1-dimethylethyl (2R,5R)-2-(aminocarbonyl)-5-(4-{[(2-fluorophenyl)methyl]oxy}phenyl)-2-[(methyloxy)methyl]-1-pyrrolidinecarboxylate (D69, 400 mg, 0.87 mmol) in a mixture of ethyl acetate (9 ml) and methanol (1 ml) at 0° C. was added AcCl (400 μl, 5.60 mmol). The mixture was stirred for 2 hours at room temperature. Two further additions of AcCl (400 μl and after 2 h another 400 μl plus additional stirring for 2 h) were required, before the reaction was complete (as shown by HPLC). The mixture was evaporated and the residue was triturated with Et2O to afford the title compound as a white solid (314 mg, 91%); Rt (HPLC) 3.71 min; MS: (ES/+) m/z: 359 [MH]+ C20H23FN2O3 requires 358; 1H NMR (500 MHz, DMSO-d6) δ (ppm): 10.05-10.25 (br.s, 1H); 8.25 (s, 1H); 8.04-8.24 (br.s, 1H); 8.02 (s, 1H); 7.52-7.65 (m, 1H); 7.38-7.51 (m, 3H); 7.21-7.33 (m, 2H); 7.07-7.17 (m, 2H); 5.19 (s, 2H); 4.59-4.76 (br.s, 1H); 4.00 (d, 1H); 3.76 (d, 1H); 3.35 (s, 3H); 2.20-2.43 (m, 2H); 2.01-2.18 (m, 1H); 1.80-1.99 (m, 1H).

Provenance & Evidence