Borane → rel-(3S,4R)-1-Benzyl-4-(4-chlorophenyl)-N-methylpyrrolidin-3-amine

HRID 910453Notes

Reaction equation

HRID 910453 reaction equation
[CH2:1]([N:8]1[CH2:12][CH:11]([C:13]2[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][CH:14]=2)[CH:10]([NH2:20])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:21]([O-])([O-])=O.[K+].[K+].ClC(OCC)=O.B>C1COCC1.O>[CH2:1]([N:8]1[CH2:12][C@@H:11]([C:13]2[CH:14]=[CH:15][C:16]([Cl:19])=[CH:17][CH:18]=2)[C@H:10]([NH:20][CH3:21])[CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 6331BoraneHCID 10928Ethyl chloroformateHCID 11430Potassium CarbonateHCID 669406161-Benzyl-4-(4-chlorophenyl)pyrrolidin-3-amine

Product 1

HCID 66940745rel-(3S,4R)-1-Benzyl-4-(4-chlorophenyl)-N-methylpyrrolidin-3-amineYield 77.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
65 °C

Procedure

To a solution of (3RS,4SR)-1-benzyl-4-(4-chloro-phenyl)-pyrrolidin-3-ylamine (1.86 g, 6.51 mmol) in THF (20 ml) was added a solution of K2CO3 (1.80 g, 13.02 mmol) in H2O (15 ml). After 10 minutes, ethyl chloroformate (0.68 ml, 7.16 mmol) was added and stirring was continued at RT for an additional 4 h. The intermediate carbamate was then extracted with Et2O, dried over Na2SO4 and concentrated under vacuo to give viscous oil. The oil was taken up in THF (20 ml) and a solution of borane in THF (1M) was added (26 ml). The reaction mixture was then heated at 65° C. over night, cooled to RT and carefully quenched with conc. HCl (5 ml). The mixture was then heated at 80° C. for 2 h, cooled to RT, concentrated under vacuo, diluted with Et2O (100 ml) and neutralized with an aqueous solution of NaHCO3. The organic phases were dried over Na2SO4 and the product purified by flash chromatography (SiO2, CH2Cl2/MeOH 9:1) to afford 1.51 g (77%) of rac-[(3S,4R)-1-benzyl-4-(4-chloro-phenyl)-pyrrolidin-3-yl]-methyl-amine as a colorless oil.

Workup

  1. waitwas continued at RT for an additional 4 h
  2. extractionThe intermediate carbamate was then extracted with Et2O
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated under vacuo
  5. customto give viscous oil
  6. temperaturecooled to RT
  7. customcarefully quenched with conc. HCl (5 ml)
  8. temperatureThe mixture was then heated at 80° C. for 2 h
  9. temperaturecooled to RT
  10. concentrationconcentrated under vacuo
  11. additiondiluted with Et2O (100 ml)
  12. dry with materialThe organic phases were dried over Na2SO4
  13. customthe product purified by flash chromatography (SiO2, CH2Cl2/MeOH 9:1)

Sources & evidence

ORD record
ord-923c50a736a04f2f9da7076caa2e8ecf
Source dataset
uspto-grants-2011_09
Patent number
US08022099B2

Reaction notes

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