4-Methylmorpholine → tert-butyl N-[(2S)-3-(cyclopenten-1-yl)-1-[methoxy(methyl)amino]-1-oxopropan-2-yl]carbamate

Temperature

0 °C

To a flask charged with (S)-2-(tert-Butoxycarbonylamino)-3-cyclopentenylpropanoic acid (55.0 g, 214 mmol) was added THF/DCM (800 mL, 1:1). The solution was cooled to 0° C. and ethyl chloroformate (24.5 mL, 257 mmol) and NMM (28.4 mL, 257 mmol) were added dropwise sequentially. After addition, the mixture was stirred at 0° C. under nitrogen for 1 h. To the other flask charged with N,O-dimethylhydroxylamine HCl (25 g, 257 mmol) was added DCM (400 mL). The mixture was cooled to 0° C. and TEA (38.7 mL, 278 mmol) was added. The resulting mixture was transferred into the former reaction flask. The reaction mixture was allowed to warm to ambient temperature and stirred overnight. The mixture was quenched with water (500 mL) and the organic phase was washed with water (500 mL), dried over anhydrous sodium sulfate, and concentrated to afford (S)-tert-butyl (3-(cyclopent-1-en-1-yl)-1-(methoxy(methyl)amino)-1-oxopropan-2-yl)carbamate as colorless oil (60 g, 93% yield), which was used in the next step without further purification.

1. additionAfter addition
2. temperatureThe mixture was cooled to 0° C.
3. temperatureto warm to ambient temperature
4. stirringstirred overnight
5. customThe mixture was quenched with water (500 mL)
6. washthe organic phase was washed with water (500 mL)
7. dry with materialdried over anhydrous sodium sulfate
8. concentrationconcentrated

ORD record

ord-624b4b83168844d8895372b7f1e2264a

Source dataset

uspto-grants-2016_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09434761B2