Reaktion #1777309

Reaktionsgleichung

1,1-dimethylethyl (2S,5R)-2-(aminocarbonyl)-5-[4-{[(2-fluorophenyl)methyl]oxy}-3-(methyloxy)phenyl]-2-methyl-1-pyrrolidinecarboxylate

AcCl

AcCl

→

title compound

Ausbeute 84.4%

(5R)-5-[4-{[(2-Fluorophenyl)methyl]oxy}-3-(methyloxy)phenyl]-2-methyl-L-prolinamide hydrochloride

Ausbeute 84.4%

Lösungsmittel

ethyl acetate

methanol

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGadditional stirring for 2 h)
2. 2
   SonstigeThe mixture was evaporated
3. 3
   Sonstigethe residue was triturated with Et2O

Vorschrift

To a solution of 1,1-dimethylethyl (2S,5R)-2-(aminocarbonyl)-5-[4-{[(2-fluorophenyl)methyl]oxy}-3-(methyloxy)phenyl]-2-methyl-1-pyrrolidinecarboxylate (D61, 110 mg, 0.24 mmol) in a mixture of ethyl acetate (2.7 ml) and methanol (0.3 ml) at 0° C. was added AcCl (110 μl, 1.54 mmol). The mixture was stirred for 1 hour at room temperature. Two further additions of AcCl (110 μl and after 1 h another 110 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 (80 mg, 84%); Rt (HPLC) 3.41 min; MS: (ES/+) m/z: 359[MH]+ C20H23FN2O3 requires 358; 1H NMR (500 MHz, DMSO-d6) δ (ppm): 9.82-10.05 (br.s, 1H); 8.02-8.27 (br.s, 1H); 8.05-8.10 (br.s, 1H); 7.80-7.90 (br.s, 1H); 7.47-7.53 (m, 1H); 7.35-7.43 (m, 1H); 7.17-7.24 (m, 2H); 7.15 (d, 1H); 7.07 (d, 1H); 6.95 (dd, 1H); 5.08 (s, 2H); 4.57-4.72 (m, 1H); 3.70-3.78 (s, 3H); 2.39-2.51 (m, 1H); 2.19-2.32 (m, 1H); 1.95-2.08 (m, 1H); 1.81-1.95 (m, 1H); 1.62 (s, 3H).

Quelle