Acetyl chloride → HCID 66700276, compound

Participants

Reaction Steps

To a solution of 1,1-dimethylethyl (2S,5R)-2-(aminocarbonyl)-5-(4-{[(2-fluorophenyl)methyl]oxy}phenyl)-2-methyl-1-pyrrolidinecarboxylate (D11, 306 mg, 0.69 mmol) in a mixture of ethyl acetate (5 ml) and methanol (0.5 ml) was added AcCl (130 μl, 2.5 eq) at 0° C. The mixture was stirred for 1 hour at room temperature. A further addition of AcCl (130 μl) was made and stirred for 30 min rt. The reaction mixture was kept overnight at −18° C. Then AcCl (another 100 μl) was added at 0° C., stirring for 15 mins, then for 1 hour at rt. The reaction was then complete (as shown by HPLC). The mixture was evaporated to afford the title compound as a white solid (246 mg, 95%); Rt (HPLC) 3.62 min; Chiral HPLC: Column: chiralpak AD-H 5 um, 250 ×4.6 mm; Mobile phase: A: n-Hexane; B: Ethanol; Gradient: isocratic 30% B; Flow rate: 0.8 ml/min; UV wavelength range: 200-400 nm; Analysis time: 20 min; ret. time: 14.3 min; MS: (ES/+) m/z: 329 [MH+]; 1H NMR (500 MHz, DMSO-d6) δ (ppm): 9.87 (br. s., 1H), 8.24 (br. s., 1H), 8.12 (s, 1H), 7.89 (s, 1H), 7.56 (t, 1H), 7.39-7.47 (m, 3H), 7.21-7.30 (m, 2H), 7.11 (d, 2H), 5.16 (s, 2H), 4.60-4.76 (m, 1H), 2.42-2.54 (m, 1H), 2.23-2.34 (m, 1H), 1.99-2.11 (m, 1H), 1.84-1.97 (m, 1H), 1.65 (s, 3H).

Provenance & Evidence