1-Bromo-3-fluorobenzene → ((S)-1-benzylpyrrolidin-3-yl)-(3-fluorophenyl)amine

A toluene solution containing 2.2 g of (S)-1-benzylpyrrolidin-3-ylamine (12.5 mmol), 2.2 g of 3-bromofluorobenzene (12.5 mmol), 0.31 g of 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (BINAP, 0.51 mmol), 0.14 g of bis(dibenzylideneacetone)palladium (Pd(dba)2, 0.22 mmol), and 1.3 g of sodium tert-butoxide (13.2 mmol) was heated under reflux under a nitrogen atmosphere for 3 hours. The reaction solution was filtered to remove insoluble matter, and ethyl acetate and water were added to the filtrate to separate the solution into layers. The organic layer was washed with water, the solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=20:1→1:1). The eluent solvent was distilled off under reduced pressure to thereby obtain 3.0 g of oily colorless ((S)-1-benzylpyrrolidin-3-yl)-(3-fluorophenyl)amine.

1. temperaturewas heated
2. temperatureunder reflux under a nitrogen atmosphere for 3 hours
3. filtrationThe reaction solution was filtered
4. customto remove insoluble matter, and ethyl acetate and water
5. additionwere added to the filtrate
6. customto separate the solution into layers
7. washThe organic layer was washed with water
8. distillationthe solvent was distilled off under reduced pressure
9. customthe residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=20:1→1:1)
10. distillationThe eluent solvent was distilled off under reduced pressure

ORD-Eintrag

ord-eb5add572dfd45ce871c0484e23348c1

Quelldatensatz

uspto-grants-2011_12

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08084442B2