Sodium hydride → (R)-3-(4-chlorobenzyloxy)-pyrrolidine-1-carboxylic acid tert-butyl ester

Temperature

0 °C

A solution of (R)-3-hydroxy-pyrrolidine-1-carboxylic acid tert-butyl ester (1.14 mmol, 1.0 eq) in THF (2.5 mL) was added to a suspension of sodium hydride (1.15 eq) in THF (2.5 mL) cooled at 0° C. and the resulting mixture was stirred for 45 min. A solution of 4-chlorobenzyl bromide (1.31 mmol, 1.15 eq) in THF (2.0 mL) was then added drop wise and reaction mixture was slowly warmed to room temperature and stirred for 18 h. The reaction mixture was quenched with water (1.0 ml) and diluted with ethyl acetate. The combined organics were dried over sodium sulfate. The crude product was purified on silica using gradient elution from hexane/ethyl acetate (10%) to hexane/ethyl acetate (30%). 1H-NMR (CDCL3) δ: 1.45 (9H, s), 1.80-2.05 (2H, m), 3.30-3.55 (4H, m), 4.05 (1H, m), 4.45 (2H, s), 7.15-7.30 (4H, m). ESI-MS m/z: 311 (M+1), UV retention time: 2.94 min.

1. customreaction mixture
2. temperaturewas slowly warmed to room temperature
3. stirringstirred for 18 h
4. customThe reaction mixture was quenched with water (1.0 ml)
5. additiondiluted with ethyl acetate
6. dry with materialThe combined organics were dried over sodium sulfate
7. customThe crude product was purified on silica using gradient elution from hexane/ethyl acetate (10%) to hexane/ethyl acetate (30%)

ORD record

ord-b68076ed52804a53a39dfdb7fd646040

Source dataset

uspto-grants-2011_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08058287B2