Ammonium Chloride → 3-Benzyloxymethyl-1-(2,6-dimethylphenyl)-5-oxo-pyrrolidine-3-carboxylic acid methyl ester

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-dimethylphenyl)-5-oxo-pyrrolidine-3-carboxylic acid methyl ester (2 g, 8.09 mmol) in THF (50 mL). The solution was stirred at −50° C. for 5 min then warmed to 0° C. and stirred for a further 5 min. After cooling back to −50° C., BOMCl (˜90% pure, 2.46 mL, 17.8 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, and the aqueous solution was extracted with EtOAc (3×75 mL). The combined organic layer were washed with water (100 mL), brine (100 mL), dried (Na2SO4) and evaporated. The residue was purified by automated flash chromatography (SiO2, 10→50% EtOAc/hexanes) to give 3-benzyloxymethyl-1-(2,6-dimethylphenyl)-5-oxo-pyrrolidine-3-carboxylic acid methyl ester (653 mg, 22% yield). LC-MS: Rt (retention time): 2.72 min, MS: (ES) m/z 368.1 (M+H+).

1. temperaturethen warmed to 0° C.
2. stirringstirred for a further 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. extractionthe aqueous solution was extracted with EtOAc (3×75 mL)
8. washThe combined organic layer were 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, 10→50% EtOAc/hexanes)

ORD record

ord-129a544de1cc431fb7380b7dd29d255a

Source dataset

uspto-grants-2014_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08716494B2