[(3S,4R)-1-benzyl-4-(4-chloro-phenyl)-pyrrolidin-3-yl]-carbamic acid methyl ester → rel-(3S,4R)-1-Benzyl-4-(4-chlorophenyl)-N-methylpyrrolidin-3-amine

HRID 587347Notes

Reaction equation

HRID 587347 reaction equation
CO[C:3](=O)[NH:4][C@H:5]1[C@H:9]([C:10]2[CH:15]=[CH:14][C:13]([Cl:16])=[CH:12][CH:11]=2)[CH2:8][N:7]([CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH2:6]1>O1CCCC1>[CH2:17]([N:7]1[CH2:8][C@@H:9]([C:10]2[CH:11]=[CH:12][C:13]([Cl:16])=[CH:14][CH:15]=2)[C@H:5]([NH:4][CH3:3])[CH2:6]1)[C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1

Participants

3

Reactant 1

HCID 67234682[(3S,4R)-1-benzyl-4-(4-chloro-phenyl)-pyrrolidin-3-yl]-carbamic acid methyl ester

Product 1

HCID 66940745rel-(3S,4R)-1-Benzyl-4-(4-chlorophenyl)-N-methylpyrrolidin-3-amineYield 80%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

To a suspension of [(3S,4R)-1-benzyl-4-(4-chloro-phenyl)-pyrrolidin-3-yl]-carbamic acid methyl ester (49.22 g, 142.7 mmol) in THF (520 mL) borane-tetrahydrofurane complex solution (1 M in tetrahydrofurane, 571 mL, 571 mmol) was added slowly over a period of 25 min. The reaction mixture was stirred for 19 h at 60° C. and then quenched with aqueous HCl (1N, 570 mL, dropwise over 60 min). The mixture was stirred for further 21 h at 60° C. After cooling to ambient temperature, tetrahydrofurane was distilled away and the residue was separated between tert-butylmethylether (1500 mL) and aqueous HCl (1N, 1000 mL). The aqueous layer was set to pH=10 with aqueous sodium carbonate (saturated, 2000 mL) and then extracted with tert-butylmethylether (twice 1500 mL). The organic layers were washed with brine (750 mL), combined and was dired over sodium sulfate. Concentration and filtration over silicagel (ethyl acetate:methanol, triethylamine=90:5:5) afforded the title compound (34.38, 80%) as a light yellow liquid. MS m/e: 301.4/303.4 [M+H]+.

Workup

  1. additionwas added slowly over a period of 25 min
  2. customquenched with aqueous HCl (1N, 570 mL
  3. waitdropwise over 60 min)
  4. stirringThe mixture was stirred for further 21 h at 60° C
  5. temperatureAfter cooling to ambient temperature
  6. distillationtetrahydrofurane was distilled away
  7. customthe residue was separated between tert-butylmethylether (1500 mL) and aqueous HCl (1N, 1000 mL)
  8. extractionextracted with tert-butylmethylether (twice 1500 mL)
  9. washThe organic layers were washed with brine (750 mL)
  10. concentrationConcentration and filtration over silicagel (ethyl acetate:methanol, triethylamine=90:5:5)

Sources & evidence

ORD record
ord-d36d96ce4a814c238c1c269cd0b0d4cf
Source dataset
uspto-grants-2016_01
Patent number
US09226916B2

Reaction notes

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