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

Temperature

-78 °C

To an oven-dried 500-mL 3-neck flask purged with nitrogen was added oxalyl chloride (5.32 mL, 60.8 mmol) and anhydrous dichloromethane (125 mL), and the solution was cooled to −78° C. A solution of anhydrous DMSO (7.30 mL, 103 mmol) in anhydrous dichloromethane (25 mL) was added dropwise from a constant-pressure addition funnel over a 20-minute period. 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 from a constant-pressure addition funnel over a 20-minute period, and then the reaction mixture was stirred at −78° C. for 30 minutes. Triethylamine (32.6 mL, 234 mmol) was added dropwise via syringe over a 5-minute period and the thick white mixture was stirred in an ice-water bath for 30 minutes. The reaction was quenched with 10% (w/v) aq. citric acid (30 mL). The mixture was partitioned in a separatory funnel between Et2O (550 mL) and 10% (w/v) aq citric acid. The layers were separated, and the organic phase was washed with water and brine. The organic phase was dried over anhydrous Na2SO4, filtered, and concentrated to afford a yellow oil (9.4 g), which was used directly in the next reaction.

1. customflask purged with nitrogen
2. stirringthe thick white mixture was stirred in an ice-water bath for 30 minutes
3. customThe reaction was quenched with 10% (w/v) aq. citric acid (30 mL)
4. customThe mixture was partitioned in a separatory funnel between Et2O (550 mL) and 10% (w/v) aq citric acid
5. customThe layers were separated
6. washthe organic phase was washed with water and brine
7. dry with materialThe organic phase was dried over anhydrous Na2SO4
8. filtrationfiltered
9. concentrationconcentrated

ORD record

ord-596755ef517a43099ca36daa4a9687bb

Source dataset

uspto-grants-2014_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08921514B2