Triethylamine → (S)-tert-Butyl (1-(methoxy(methyl)amino)-1-oxopropan-2-yl)carbamate

To a solution of Boc-alanine (20 grams, 105.7 mmol) in dichloromethane (170 ml) was added HOBT (14.28 g, 105.7 mmol) and N, O-dimethylhydroxylamine hydrochloride (10.31 g, 105.7 mmol). The mixture was chilled with an ice water bath then triethylamine (30 ml, 211.4 mmol) and 1,3-dicyclohexylcarbodiimide (21.81 g, 105.7 mmol) were added. The reaction was stirred in the ice water bath for 1 hour and then allowed to warm to room temperature overnight. The crude reaction was then chilled in an ice water bath and the precipitate filtered. The resulting organic solution was then washed twice with 1N aqueous sodium hydroxide (50 mL), twice with 10% aqueous citric acid (50 mL), and once with brine. The solution was then dried over anhydrous sodium sulfate, filtered, and the solvent evaporated. The resulting residue was purified by chromatography on a normal phase silica gel column with 30-100% ethyl acetate in hexanes. Fractions containing clean product were combined and the solvent evaporated to give the title compound (20 g, 81%): ES-MS (m/z) 233.2 [M+1]+.

1. temperatureThe mixture was chilled with an ice water bath
2. customThe crude reaction
3. temperaturewas then chilled in an ice water bath
4. filtrationthe precipitate filtered
5. washThe resulting organic solution was then washed twice with 1N aqueous sodium hydroxide (50 mL), twice with 10% aqueous citric acid (50 mL)
6. dry with materialThe solution was then dried over anhydrous sodium sulfate
7. filtrationfiltered
8. customthe solvent evaporated
9. customThe resulting residue was purified by chromatography on a normal phase silica gel column with 30-100% ethyl acetate in hexanes
10. additionFractions containing clean product
11. customthe solvent evaporated

ORD record

ord-1d5ce1fa38924a47896df937bb8a33e6

Source dataset

uspto-grants-2012_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08101588B2