Dimethyl Sulfoxide → 3-Oxo-azetidine-1-carboxylic acid tert-butyl ester

Temperature

-78 °C

To a −78° C. solution of 2M oxalyl chloride (31.8 mL, 63.5 mmol) in 200 mL DCM was added DMSO (9.01 mL, 127 mmol), followed by the slow addition by addition funnel of a solution of tert-butyl 3-hydroxyazetidine-1-carboxylate (10.0 g, 57.7 mmol) in 200 mL DCM. The cloudy reaction mixture was stirred at −78° C. for 15 minutes, then a solution triethylamine (32.2 mL, 231 mmol) in 40 mL DCM was added slowly by addition funnel. The reaction mixture was stirred another 15 minutes, the bath was removed, and the reaction was allowed to warm to ambient temperature and stirred for 15 hours. Water and brine were added, and the mixture was extracted with DCM. The combined extracts were dried (Na2SO4), filtered and concentrated. The crude was purified on silica gel (3-20% ethyl acetate in hexanes gradient) to give the desired product (9.0 g, 91.1% yield) as a white solid.

1. customThe cloudy reaction mixture
2. stirringThe reaction mixture was stirred another 15 minutes
3. customthe bath was removed
4. temperatureto warm to ambient temperature
5. stirringstirred for 15 hours
6. additionWater and brine were added
7. extractionthe mixture was extracted with DCM
8. dry with materialThe combined extracts were dried (Na2SO4)
9. filtrationfiltered
10. concentrationconcentrated
11. customThe crude was purified on silica gel (3-20% ethyl acetate in hexanes gradient)

ORD record

ord-34e252f195f24c65ba9bd08aa5af687d

Source dataset

uspto-grants-2015_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08987251B2