Acetyl chloride → HCID 66700299, compound

HRID 1717213Notes

Reaction equation

HRID 1717213 reaction equation
[NH2:1][C:2]([C@:4]1([CH3:33])[CH2:8][CH2:7][C@H:6]([C:9]2[CH:14]=[CH:13][C:12]([O:15][CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[F:23])=[C:11]([O:24][CH3:25])[CH:10]=2)[N:5]1C(OC(C)(C)C)=O)=[O:3].C([Cl:37])(C)=O>C(OCC)(=O)C.CO>[ClH:37].[F:23][C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=1[CH2:16][O:15][C:12]1[CH:13]=[CH:14][C:9]([C@@H:6]2[NH:5][C@:4]([CH3:33])([C:2]([NH2:1])=[O:3])[CH2:8][CH2:7]2)=[CH:10][C:11]=1[O:24][CH3:25]

Participants

5

Reactant 2

HCID 6367Acetyl chloride2×HCID 59468964HCID 59468964, compound

Product 1

HCID 66700299HCID 66700299, compoundYield 84.4%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

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).

Workup

  1. stirringadditional stirring for 2 h)
  2. customThe mixture was evaporated
  3. customthe residue was triturated with Et2O

Sources & evidence

ORD record
ord-7a271e6c07154283b3456af00df997f7
Source dataset
uspto-grants-2010_09
Patent number
US07803833B2

Reaction notes

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