(3S)-(-)-3-(tert-Butoxycarbonylamino)pyrrolidine → tert-butyl (S)-1-(2-((trans)-2-(3'-(trifluoromethyl)biphenyl-4-yl)cyclopropylamino)ethyl)pyrrolidin-3-ylcarbamate

HRID 535804Notes

Reaction equation

HRID 535804 reaction equation
Cl[CH2:2][CH2:3][NH:4][C@@H:5]1[CH2:7][C@H:6]1[C:8]1[CH:13]=[CH:12][C:11]([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([C:20]([F:23])([F:22])[F:21])[CH:15]=2)=[CH:10][CH:9]=1.[NH:24]1[CH2:28][CH2:27][C@H:26]([NH:29][C:30](=[O:36])[O:31][C:32]([CH3:35])([CH3:34])[CH3:33])[CH2:25]1>CN(C=O)C>[F:21][C:20]([F:23])([F:22])[C:16]1[CH:15]=[C:14]([C:11]2[CH:12]=[CH:13][C:8]([C@@H:6]3[CH2:7][C@H:5]3[NH:4][CH2:3][CH2:2][N:24]3[CH2:28][CH2:27][C@H:26]([NH:29][C:30](=[O:36])[O:31][C:32]([CH3:34])([CH3:33])[CH3:35])[CH2:25]3)=[CH:9][CH:10]=2)[CH:19]=[CH:18][CH:17]=1

Participants

4

Reactant 2

HCID 1514396(3S)-(-)-3-(tert-Butoxycarbonylamino)pyrrolidineHCID 89123862(trans)-N-(2-chloroethyl)-2-(3'-(trifluoromethyl)biphenyl-4-yl)cyclopropanamine

Product 1

HCID 86673372tert-butyl (S)-1-(2-((trans)-2-(3'-(trifluoromethyl)biphenyl-4-yl)cyclopropylamino)ethyl)pyrrolidin-3-ylcarbamateYield 37%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (trans)-N-(2-chloroethyl)-2-(3′-(trifluoromethyl)biphenyl-4-yl)cyclopropanamine (750 mg, 2.21 mmol) in dry DMF (7.5 mL), (S)-tert-butyl pyrrolidin-3-ylcarbamate (864 mg g, 4.64 mmol) was added and stirred at RT for 48 h. After completion, the reaction mixture was poured into ice water (25 mL), extracted with EtOAc (2×20 mL). The combined extracts were washed with water (25 mL), brine (20 mL), dried over anhydrous Na2SO4, filtered and evaporated. The crude residue was purified by column chromatography (SiO2) using MeOH: CHCl3(4:96) to get tert-butyl (S)-1-(2-((trans)-2-(3′-(trifluoromethyl)biphenyl-4-yl)cyclopropylamino)ethyl)pyrrolidin-3-ylcarbamate (400 mg, 37%) as a white solid.

Workup

  1. extractionextracted with EtOAc (2×20 mL)
  2. washThe combined extracts were washed with water (25 mL), brine (20 mL)
  3. dry with materialdried over anhydrous Na2SO4
  4. filtrationfiltered
  5. customevaporated
  6. customThe crude residue was purified by column chromatography (SiO2)

Sources & evidence

ORD record
ord-8c29d5dc90f64551bb0ac83e0d7cfd57
Source dataset
uspto-grants-2014_10
Patent number
US08859555B2

Reaction notes

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