Acetyl chloride → 2-(tert-Butoxycarbonyl-cyclopropyl-amino)-3-oxo-butyric acid ethyl ester
Reaction equation
[CH2:1]([O:3][C:4](=[O:17])[CH2:5][N:6]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH:7]1[CH2:9][CH2:8]1)[CH3:2].[C:18](Cl)(=[O:20])[CH3:19]>C1COCC1>[CH2:1]([O:3][C:4](=[O:17])[CH:5]([N:6]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH:7]1[CH2:8][CH2:9]1)[C:18](=[O:20])[CH3:19])[CH3:2]Participants
Procedure
To solution of 63 ml (1 M in THF, 63 mmol) of lithium hexamethyldisilylazide cooled to −78° C. under Ar was added, drop wise, a solution of 7.3 g (30 mmol) of (tert-butoxycarbonyl-cyclopropyl-amino)-acetic acid ethyl ester in 10 ml of THF. The mixture was brought to −40° C. and stirred for 1 h. 2.3 ml (30 mmol) of acetyl chloride was then added and the mixture allowed to reach room temperature over 1 h after which time the reaction was quenched by addition to 10% citric acid solution. The mixture was then extracted with EtOAc, dried with sodium sulfate and concentrated. Purification by flash column chromatography [n-heptane/EtOAc 1:9 to 2:8] afforded 5.8 g (67%) of the title compound as colorless oil, partially contaminated with the starting material. MS: 286.1 (MH+).
Workup
- additionwas added
- customwas brought to −40° C.
- waitto reach room temperature over 1 h
- customafter which time the reaction was quenched by addition to 10% citric acid solution
- extractionThe mixture was then extracted with EtOAc
- dry with materialdried with sodium sulfate
- concentrationconcentrated
- customPurification by flash column chromatography [n-heptane/EtOAc 1:9 to 2:8]
Sources & evidence
- ORD record
- ord-bea9f7b388214100a27759adddd13ef4
- Source dataset
- uspto-grants-2011_05
- Patent number
- US07935707B2
Reaction notes
Loading…