Acetyl chloride → HCID 66700276, compound

HRID 1717209Notes

Reaction equation

HRID 1717209 reaction equation
[NH2:1][C:2]([C@:4]1([CH3:31])[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:35])(C)=O>C(OCC)(=O)C.CO>[ClH:35].[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]([CH3:31])([C:2]([NH2:1])=[O:3])[CH2:8][CH2:7]2)=[CH:10][CH:11]=1

Participants

5

Reactant 2

HCID 6367Acetyl chloride3×HCID 59468932HCID 59468932, compound

Product 1

HCID 66700276HCID 66700276, compoundYield 95%

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}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: 200400 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).

Workup

  1. stirringstirred for 30 min rt
  2. waitThe reaction mixture was kept overnight at −18° C
  3. stirringstirring for 15 mins
  4. waitfor 1 hour at rt
  5. customThe mixture was evaporated

Sources & evidence

ORD record
ord-c46bcf5ccf7f4c36bec61ce1929fef56
Source dataset
uspto-grants-2010_09
Patent number
US07803833B2

Reaction notes

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