(S)-tert-butyl 3-formylpyrrolidine-1-carboxylate → (R)-tert-Butyl 3-vinylpyrrolidine-1-carboxylate

A slurry of methyltriphenylphosphonium bromide (16.1 g, 45.2 mmol, 3.0 eq.) in THF (50 mL) was cooled to −78° C. 1M Sodium bis(trimethylsilyl)amide in THF (38.0 mL, 2.8 eq.) was added and the mixture was stirred for 30 minutes. A solution of (S)-3-formylpyrrolidine-1-carboxylic acid t-butyl ester (3.0 g, 15.0 mmol, 1.0 eq.) in THF (10 mL) was slowly added and the mixture was stirred at −78° C. for 2 hours. The mixture was warmed to room temperature over 3 hours and the reaction was quenched with half saturated NH4Cl (50 mL). The organic layer was washed with saturated aqueous NaCl (50 mL). The organic layer was collected, dried over MgSO4, filtered, and concentrated. The resulting oil was slurried in hexanes (50 mL) and the precipitate was filtered off. The filtrate was concentrated, diluted with hexanes (25 mL), and chilled at −20° C. overnight. The precipitate was filtered off and the filtrate was purified by column chromatography (0-100% EtOAc in hexanes) to yield (R)-3-vinylpyrrolidine-1-carboxylic acid t-butyl ester as an oil (2.1 g).

1. stirringthe mixture was stirred at −78° C. for 2 hours
2. customthe reaction was quenched with half saturated NH4Cl (50 mL)
3. washThe organic layer was washed with saturated aqueous NaCl (50 mL)
4. customThe organic layer was collected
5. dry with materialdried over MgSO4
6. filtrationfiltered
7. concentrationconcentrated
8. filtrationthe precipitate was filtered off
9. concentrationThe filtrate was concentrated
10. additiondiluted with hexanes (25 mL)
11. temperaturechilled at −20° C. overnight
12. filtrationThe precipitate was filtered off
13. customthe filtrate was purified by column chromatography (0-100% EtOAc in hexanes)

ORD record

ord-2024f040511f495fbf684eae3e8dc6e3

Source dataset

uspto-grants-2014_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08729119B2