Borane → (3S,4R)-1-benzyl-4-(3,4-dichlorophenyl)-N-methylpyrrolidin-3-amine

HRID 587306Notes

Reaction equation

HRID 587306 reaction equation
[CH2:1]([N:8]1[CH2:12][CH:11]([C:13]2[CH:18]=[CH:17][C:16]([Cl:19])=[C:15]([Cl:20])[CH:14]=2)[CH:10]([NH2:21])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:22]([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:18]=[CH:17][C:16]([Cl:19])=[C:15]([Cl:20])[CH:14]=2)[C@H:10]([NH:21][CH3:22])[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 672341221-Benzyl-4-(3,4-dichlorophenyl)pyrrolidin-3-amine

Product 1

HCID 67233850(3S,4R)-1-benzyl-4-(3,4-dichlorophenyl)-N-methylpyrrolidin-3-amineYield 51.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
65 °C

Procedure

To a solution of rac-(3S,4R)-1-benzyl-4-(3,4-dichloro-phenyl)-pyrrolidin-3-ylamine (0.54 g, 1.68 mmol) in THF (5 mL) was added a solution of K2CO3 (0.46 g, 3.36 mmol) in H2O (3 mL). After 10 minutes, ethyl chloroformate (0.18 mL, 1.85 mmol) was added and stirring was continued at ambient temperature for an additional 2 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 (5 mL) and a solution of borane in THF (1M) was added (6.7 mL). The reaction mixture was then heated at 65° C. over night, cooled to ambient temperature and carefully quenched with conc. HCl (5 mL). The mixture was then heated at 80° C. for 2 h, cooled to ambient temperature, concentrated under vacuo, diluted with Et2O (20 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 0.29 g (51%) of rac-[(3S,4R)-1-benzyl-4-(3,4-dichloro-phenyl)-pyrrolidin-3-yl]-methyl-amine as a colorless oil. ES-MS m/e: 335.3 (M+H+).

Workup

  1. waitwas continued at ambient temperature for an additional 2 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 ambient temperature
  7. customcarefully quenched with conc. HCl (5 mL)
  8. temperatureThe mixture was then heated at 80° C. for 2 h
  9. temperaturecooled to ambient temperature
  10. concentrationconcentrated under vacuo
  11. additiondiluted with Et2O (20 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-4a519c4b300c4e288a8eb3eba8978885
Source dataset
uspto-grants-2016_01
Patent number
US09226916B2

Reaction notes

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