Acetyl chloride → HCID 66700205, compound

HRID 1690129Notes

Reaction equation

HRID 1690129 reaction equation
[NH2:1][C:2]([C@:4]1([CH2:31][O:32][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])=[CH:11][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]([CH2:31][O:32][CH3:33])([C:2]([NH2:1])=[O:3])[CH2:8][CH2:7]2)=[CH:10][CH:11]=1

Participants

5

Reactant 2

HCID 6367Acetyl chloride2×HCID 59468977HCID 59468977, compound

Product 1

HCID 66700205HCID 66700205, compoundYield 91.4%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

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).

Workup

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

Sources & evidence

ORD record
ord-4cecc6a396aa420f91714a4e1680ef33
Source dataset
uspto-grants-2012_04
Patent number
US08153623B2

Reaction notes

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