Acetic Anhydride → 2-[Cyclopropyl-(4-trifluoromethoxy-benzoyl)-amino]-3-oxo-butyric acid ethyl ester

HRID 545337Notes

Reaction equation

HRID 545337 reaction equation
[CH2:1]([O:3][C:4](=[O:23])[CH2:5][N:6]([CH:20]1[CH2:22][CH2:21]1)[C:7](=[O:19])[C:8]1[CH:13]=[CH:12][C:11]([O:14][C:15]([F:18])([F:17])[F:16])=[CH:10][CH:9]=1)[CH3:2].[C:24](OC(=O)C)(=[O:26])[CH3:25]>C1COCC1.CCOC(C)=O>[CH2:1]([O:3][C:4](=[O:23])[CH:5]([N:6]([CH:20]1[CH2:22][CH2:21]1)[C:7](=[O:19])[C:8]1[CH:9]=[CH:10][C:11]([O:14][C:15]([F:16])([F:17])[F:18])=[CH:12][CH:13]=1)[C:24](=[O:26])[CH3:25])[CH3:2]

Participants

5

Reactant 2

HCID 7918Acetic AnhydrideHCID 67133328[Cyclopropyl-(4-trifluoromethoxy-benzoyl)-amino]-acetic acid ethyl ester

Product 1

HCID 671333462-[Cyclopropyl-(4-trifluoromethoxy-benzoyl)-amino]-3-oxo-butyric acid ethyl esterYield 13.4%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 6.6 ml (1 M in THF, 7 mmol) of lithium hexamethyldisilylazide cooled to −78° C. under Ar was added, drop wise, a solution of 2.0 g (6 mmol) of [cyclopropyl-(4-trifluoromethoxy-benzoyl)-amino]-acetic acid ethyl ester in 10 ml of THF. The mixture was stirred for 1 h before 0.7 g of acetic anhydride was added and the mixture was allowed to reach room temperature. After 2 h the reaction was diluted with EtOAc, washed with saturated ammonium chloride solution, the organic phase dried with sodium sulfate and concentrated. Purification by flash column chromatography [n-heptane/EtOAc 1:9 to 3:7] afforded 0.3 g (13%) of the title compound as a colorless oil. MS: 374.2 (MH+).

Workup

  1. additionwas added
  2. additionwas added
  3. customto reach room temperature
  4. washwashed with saturated ammonium chloride solution
  5. dry with materialthe organic phase dried with sodium sulfate
  6. concentrationconcentrated
  7. customPurification by flash column chromatography [n-heptane/EtOAc 1:9 to 3:7]

Sources & evidence

ORD record
ord-04d500085abb4729b06bc6a641f4f90b
Source dataset
uspto-grants-2011_05
Patent number
US07935707B2

Reaction notes

Loading…