Acetic Acid → 2-(2-bromophenyl)pyrrolidine

Temperature

-65 °C

5-(2-Bromophenyl)-3,4-dihydro-2H-pyrrole (compound 8; 393 mmol, 88 g) was dissolved in methanol (1300 mL), then the acetic acid (330 mL) was added and the solution cooled to −65° C. under a nitrogen atmosphere. Sodium borohydride (589 mmol, 22.28 g) was added portionwise over 1 hour. The reaction was stirred at −65° C. for 30 minutes, then the cooling bath was removed and the reaction mixture temperature was allowed to rise to room temperature. The bulk of the methanol was removed under vacuum then 5N HCl (950 mL) was added and the solution extracted with ether (2×500 mL). The aqueous solution was then basified with sodium hydroxide pellets (310 g) with ice-bath cooling, maintaining the reaction temperature less than 30° C. The basified aqueous was then extracted with ethyl acetate (3×800 mL), the combined organics washed with brine (800 mL), dried with sodium sulfate, evaporated and chromatographed on 1 Kg of silica gel eluting with 19:1 to 9:1 methylene chloride-ethanol to give 2-(2-bromophenyl)pyrrolidine (68.5 g).

1. customthe cooling bath was removed
2. customto rise to room temperature
3. customThe bulk of the methanol was removed under vacuum
4. addition5N HCl (950 mL) was added
5. extractionthe solution extracted with ether (2×500 mL)
6. customThe aqueous solution was then basified with sodium hydroxide pellets (310 g) with ice-bath
7. temperaturecooling
8. temperaturemaintaining the reaction temperature less than 30° C
9. extractionThe basified aqueous was then extracted with ethyl acetate (3×800 mL)
10. washthe combined organics washed with brine (800 mL)
11. dry with materialdried with sodium sulfate
12. customevaporated
13. customchromatographed on 1 Kg of silica gel eluting with 19:1 to 9:1 methylene chloride-ethanol

ORD record

ord-8360ef0d3d3c4a3795185eee15c14332

Source dataset

uspto-grants-2012_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08188123B2