Tetrahydrofuran → HCID 58218800, compound

Temperature

-50 °C

LHMDS (1 M solution in THF, 9.72 mL, 9.72 mmol) was added slowly to a cooled (−50° C.) solution of 1-(2,6-dimethyl-phenyl)-5-oxo-pyrrolidine-3-carboxylic acid methyl ester (2 g, 8.1 mmol) in THF (50 mL). Stirred at −50° C. for 5 min then warmed to 0° C. and stirred further for 5 min. After cooling back to −50° C., (CH2O)n (1.2 g, 40.5 mmol) was added and the resulting reaction mixture was warmed to room temperature and stirred for 2 h. Saturated aqueous NH4Cl solution (25 mL) was added, extracted with EtOAc (3×75 mL). The combined organic layer was washed with water (100 mL), brine (100 mL), dried (Na2SO4) and evaporated. The residue was purified by automated flash chromatography (SiO2, 20→50% EtOAc/hexanes) to give 1-(2,6-dimethyl-phenyl)-3-hydroxymethyl-5-oxo-pyrrolidine-3-carboxylic acid methyl ester (762 mg, 34% yield). LC-MS: Rt (retention time): 0.9 min, MS: (ES) m/z 278.1 (M+H+).

1. temperaturethen warmed to 0° C.
2. stirringstirred further for 5 min
3. temperatureAfter cooling back to −50° C.
4. customthe resulting reaction mixture
5. temperaturewas warmed to room temperature
6. stirringstirred for 2 h
7. extractionextracted with EtOAc (3×75 mL)
8. washThe combined organic layer was washed with water (100 mL), brine (100 mL)
9. dry with materialdried (Na2SO4)
10. customevaporated
11. customThe residue was purified by automated flash chromatography (SiO2, 20→50% EtOAc/hexanes)

ORD record

ord-f9602ea6bd7142af9ec1eece754c103c

Source dataset

uspto-grants-2012_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08293925B2