Citric Acid → 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 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 20-min 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 20-min period, then stirred reaction mixture at −78° C. for 30 min. Added triethylamine (32.6 mL, 234 mmol) dropwise via syringe over a 5-min period and stirred the thick white mixture in an ice-water bath for 30 min. Quenched reaction with 10% (w/v) aq. citric acid (30 mL), poured reaction into a separatory funnel with Et2O (550 mL) and 10% (w/v) aq citric acid, separated layers, and washed organic phase with water and brine. Dried the organic phase 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. customreaction mixture at −78° C. for 30 min
3. stirringstirred the thick white mixture in an ice-water bath for 30 min
4. customQuenched
5. customreaction with 10% (w/v) aq. citric acid (30 mL)
6. additionpoured
7. customseparated layers
8. washwashed organic phase with water and brine
9. dry with materialDried the organic phase over anhydrous Na2SO4
10. filtrationfiltered
11. concentrationconcentrated

ORD record

ord-467e6bc01269439fa735346ff56d2713

Source dataset

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08691938B2