Diisopropylamine → (R)-2-[2-(3-Chloro-phenyl)-2-oxo-ethyl]-pyrrolidine-1-carboxylic acid tert-butyl ester

Temperature

-70 °C

Diisopropylamine (764 uL, 5.4 mmol) was dissolved in THF (15 mL) under nitrogen and cooled to −70° C. Then a 1.6 M solution of butyllithium in hexane (3.4 mL, 5.4 mmol) was added and stirring at −70° C. was continued for 15 min. Then a solution of (3-chloro-phenyl)-trimethylsilanyloxy-acetonitrile (1.18 g, 4.9 mmol) in THF (5 mL) was added and stirring at −70° C. was continued for 30 min, producing a yellow color. Then a solution of (S)-2-iodomethyl-pyrrolidine-1-carboxylic acid tert-butyl ester (1.53 g, 4.9 mmol) in THF (5 mL) was added and stirring at −70° C. was continued for 5 h and then allowed to warm up to 20° C. and stirred overnight. The mixture was extracted with AcOEt, 1 M citric acid, and 50% NaCl. The crude product was purified by flash chromatography on silica gel with a heptane/AcOEt gradient 0-15%. One obtained 500 mg (31%) of a yellow oil. MS: m/z=224 [M+].

1. stirringstirring at −70° C.
2. waitwas continued for 30 min
3. customproducing a yellow color
4. stirringstirring at −70° C.
5. waitwas continued for 5 h
6. temperatureto warm up to 20° C.
7. stirringstirred overnight
8. extractionThe mixture was extracted with AcOEt, 1 M citric acid, and 50% NaCl
9. customThe crude product was purified by flash chromatography on silica gel with a heptane/AcOEt gradient 0-15%

ORD record

ord-08f4ae8f84d840f4b1b84bd8b619e45d

Source dataset

uspto-grants-2009_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07498339B2