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

HRID 1966020Notes

Reaction equation

HRID 1966020 reaction equation
[CH2:1]([N:8]1[CH2:12][CH2:11][C@H:10]([NH2:13])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Br[C:15]1[CH:16]=[C:17]([F:21])[CH:18]=[CH:19][CH:20]=1.CC(C)([O-])C.[Na+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(C)C=CC=CC=1>[CH2:1]([N:8]1[CH2:12][CH2:11][C@H:10]([NH:13][C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([F:21])[CH:16]=2)[CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 3

HCID 140821-Bromo-3-fluorobenzeneHCID 1519353(3S)-(+)-1-Benzyl-3-aminopyrrolidineHCID 23676156Sodium t-butoxide

Product 1

HCID 29080908((S)-1-benzylpyrrolidin-3-yl)-(3-fluorophenyl)amineYield 88.8%

Reagents, catalysts & solvents 3

HCID 634876Binap, (A+-)-CatalystHCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladiumCatalystHCID 1140TolueneSolvent

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-0d6db9c32b4d449d9d7d80e9a02bf128
Source dataset
uspto-grants-2013_04
Patent number
US08420623B2

Reaction notes

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