Dimethyl Sulfoxide → tert-butyl (2S)-2-formylpyrrolidine-1-carboxylate

Temperature

-78 °C

Oxalyl chloride (5.32 mL, 60.8 mmol) and anhydrous dichloromethane (125 mL) were combined under nitrogen, and the solution was cooled to −78° C. A solution of anhydrous dimethyl sulfoxide (7.30 mL, 103 mmol) in anhydrous dichloromethane (25 mL) was added dropwise over 20 minutes. A solution of (S)-tert-butyl 2-(hydroxymethyl)pyrrolidine-1-carboxylate (9.41 g, 46.8 mmol) in anhydrous dichloromethane (50 mL) was added dropwise over 20 minutes, and then the reaction mixture was stirred at −78° C. for 30 minutes. Triethylamine (32.6 mL, 234 mmol) was then added dropwise over a 5 minutes, and the reaction mixture was stirred in an ice-water bath for 30 minutes. The reaction was quenched with 10% (w/v) aqueous citric acid (30 mL), and the resultant mixture was partitioned between diethyl ether (550 mL) and 10% (w/v) aqueous citric acid. The organic phase was subsequently washed with water and brine. The organic phase was dried over anhydrous Na2SO4, filtered, and concentrated to afford the title compound (9.4 g), which was used directly in the next reaction.

1. stirringthe reaction mixture was stirred in an ice-water bath for 30 minutes
2. customThe reaction was quenched with 10% (w/v) aqueous citric acid (30 mL)
3. customthe resultant mixture was partitioned between diethyl ether (550 mL) and 10% (w/v) aqueous citric acid
4. washThe organic phase was subsequently washed with water and brine
5. dry with materialThe organic phase was dried over anhydrous Na2SO4
6. filtrationfiltered
7. concentrationconcentrated

ORD record

ord-6c98198e6a304ddd98b04a82a476c275

Source dataset

uspto-grants-2016_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09394279B2