Borane → HCID 66940734, compound

HRID 1365916Notes

Reaction equation

HRID 1365916 reaction equation
[CH2:1]([N:8]1[CH2:12][CH:11]([C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][C:14]=2[CH3:20])[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]([F:19])=[CH:15][C:14]=2[CH3:20])[C@H:10]([NH:21][CH3:22])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 6331BoraneHCID 10928Ethyl chloroformateHCID 11430Potassium CarbonateHCID 669409853-Pyrrolidinamine, 4-(4-fluoro-2-methylphenyl)-1-(phenylmethyl)-

Product 1

HCID 66940734HCID 66940734, compoundYield 56.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
65 °C

Procedure

To a solution of rac-(3S,4R)-1-benzyl-4-(4-fluoro-2-methyl-phenyl)-pyrrolidin-3-ylamine (130 mg, 0.46 mmol) in THF (6 ml) was added a solution of K2CO3 (126 mg, 0.91 mmol) in H2O (2 ml). After 10 minutes, ethyl chloroformate (0.05 ml, 0.48 mmol) was added and stirring was continued at RT 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 (1.9 ml). The reaction mixture was then heated at 65° C. over night, cooled to RT and carefully quenched with conc. HCl (2 ml). The mixture was then heated at 80° C. for 2 h, cooled to RT, concentrated under vacuo, diluted with Et2O (30 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 77 mg (56%) of rac-[(3S,4R)-1-benzyl-4-(4-fluoro-2-methyl-phenyl)-pyrrolidin-3-yl]-methyl-amine as a colorless oil. ES-MS m/e: 299.3 (M+H+).

Workup

  1. waitwas continued at RT 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 RT
  7. customcarefully quenched with conc. HCl (2 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 (30 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-0dc0433cd0e847e9a7dfec7a32879b7a
Source dataset
uspto-grants-2011_02
Patent number
US07893062B2

Reaction notes

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