Triethylamine → 2-Bromo-2-methyl-propionic acid pyrrolidin-1-yl ester

温度

0 °C

A solution of N-hydroxysuccinimide (NHS) (3.0 g, 26 mmol) in dry methylene chloride (300 mL) was stirred under an inert (argon or nitrogen) atmosphere. Triethylamine (7.3 mL, 52 mmol) was added, the mixture was cooled to 0° C., and 2-bromo-2-methylpropionyl bromide (3.9 mL, 31 mmol) was added dropwise over a period of 15 minutes. The mixture was stirred for 1 hour at 0° C., then warmed to room temperature and stirred overnight. Most of the solvent was removed by evaporation, and the remaining mixture was diluted with cold water (400 mL), and extracted with diethyl ether (3×30 mL), then washed with aqueous potassium carbonate (3×30 mL) and 1M HCl(aq) (3×30 mL). The organic layer was dried over anhydrous magnesium sulfate, then filtered and concentrated to give a brown solid. Crystallization from ethyl acetate gave the desired product as a white powder (2.62 g, 39%). 1H NMR (CDCl3) δ (ppm) 2.09 (s, 6H, CH3)2Br), 2.88 (s, 4H, HNHS); 13C NMR (CDCl3) δ (ppm) 25.7 (CNHS), 30.8 (C(CH3)2Br), 51.3 (C(CH3)2Br), 167.6 (C═O), 168.7 (CNHS═O).

1. temperaturewarmed to room temperature
2. stirringstirred overnight
3. customMost of the solvent was removed by evaporation
4. additionthe remaining mixture was diluted with cold water (400 mL)
5. extractionextracted with diethyl ether (3×30 mL)
6. washwashed with aqueous potassium carbonate (3×30 mL) and 1M HCl(aq) (3×30 mL)
7. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
8. filtrationfiltered
9. concentrationconcentrated
10. customto give a brown solid
11. customCrystallization from ethyl acetate

ORDレコード

ord-b7113734ed2a43ea818c8f6cdeac157f

出典データセット

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08846021B2