Pyridine → (3SR,4RS)-3-(3,4-Dichloro-phenyl)-4-[(3-fluoro-4-trifluoromethyl-benzyl)-methyl-amino]-pyrrolidine-1-carbonyl chloride

HRID 910460Notes

Reaction equation

HRID 910460 reaction equation
ClC(Cl)(OC(=O)[O:6][C:7]([Cl:10])(Cl)Cl)Cl.[Cl:13][C:14]1[CH:15]=[C:16]([CH:21]2[CH2:25][NH:24][CH2:23][CH:22]2[N:26]([CH2:28][C:29]2[CH:34]=[CH:33][C:32]([C:35]([F:38])([F:37])[F:36])=[C:31]([F:39])[CH:30]=2)[CH3:27])[CH:17]=[CH:18][C:19]=1[Cl:20].N1C=CC=CC=1>C(Cl)Cl>[Cl:13][C:14]1[CH:15]=[C:16]([CH:21]2[CH:22]([N:26]([CH2:28][C:29]3[CH:34]=[CH:33][C:32]([C:35]([F:37])([F:38])[F:36])=[C:31]([F:39])[CH:30]=3)[CH3:27])[CH2:23][N:24]([C:7]([Cl:10])=[O:6])[CH2:25]2)[CH:17]=[CH:18][C:19]=1[Cl:20]

Participants

5

Reactant 3

HCID 1049PyridineHCID 94429TriphosgeneHCID 75231672[(3RS,4SR)-4-(3,4-Dichloro-phenyl)-pyrrolidin-3-yl]-(3-fluoro-4-trifluoromethyl-benzyl)-methyl-amine

Product 1

HCID 72253484(3SR,4RS)-3-(3,4-Dichloro-phenyl)-4-[(3-fluoro-4-trifluoromethyl-benzyl)-methyl-amino]-pyrrolidine-1-carbonyl chlorideYield 137.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a stirred solution of carbonic acid ditrichloromethyl ester (triphosgene) (37 mg, 0.125 mmol) in CH2Cl2 (10 ml) at −78° C., was added a solution of [(3RS,4SR)-4-(3,4-Dichloro-phenyl)-pyrrolidin-3-yl]-(3-fluoro-4-trifluoromethyl-benzyl)-methyl-amine (Intermediate VIII-1), (130 mg, 0.31 mmol) and pyridine (0.05 ml, 0.68 mmol) in CH2Cl2 (5 ml) over 30 minutes. The temperature was raised to RT, and stirring was continued for 2 hours. The organic phase was washed with H2O, dried over Na2SO4. Purification by flash chromatography (SiO2, EtOAc/Hx 1:2) yielded 83 mg (55%) of the title compound as a light yellow oil.

Workup

  1. washThe organic phase was washed with H2O
  2. dry with materialdried over Na2SO4
  3. customPurification by flash chromatography (SiO2, EtOAc/Hx 1:2)

Sources & evidence

ORD record
ord-a631d88cbdf54430becef464a36ba409
Source dataset
uspto-grants-2011_09
Patent number
US08022099B2

Reaction notes

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