Pyridine → (3SR,4RS)-3-(3,4-Dichloro-phenyl)-4-[(SR)-1-(5-trifluoromethyl-pyridin-2-yloxy)-ethyl]-pyrrolidine-1-carbonyl chloride

HRID 1158668Notes

Reaction equation

HRID 1158668 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[CH:26]([O:28][C:29]2[CH:34]=[CH:33][C:32]([C:35]([F:38])([F:37])[F:36])=[CH:31][N:30]=2)[CH3:27])[CH:17]=[CH:18][C:19]=1[Cl:20].N1C=CC=CC=1.CCOC(C)=O>C(Cl)Cl>[Cl:13][C:14]1[CH:15]=[C:16]([CH:21]2[CH:22]([CH:26]([O:28][C:29]3[CH:34]=[CH:33][C:32]([C:35]([F:38])([F:36])[F:37])=[CH:31][N: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

6

Reactant 4

HCID 1049PyridineHCID 8857Ethyl AcetateHCID 94429TriphosgeneHCID 669991102-{(SR)-1-[(3RS,4SR)-4-(3,4-Dichloro-phenyl)-pyrrolidin-3-yl]-ethoxy}-5-trifluoromethyl-pyridine

Product 1

HCID 86628182(3SR,4RS)-3-(3,4-Dichloro-phenyl)-4-[(SR)-1-(5-trifluoromethyl-pyridin-2-yloxy)-ethyl]-pyrrolidine-1-carbonyl chlorideYield 104%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a stirred solution of carbonic acid ditrichloromethyl ester (triphosgene) (22 mg 0.074 mmol) in CH2Cl2 (3 mL) at −78° C., was added a solution of 2-{(SR)-1-[(3RS,4SR)-4-(3,4-dichloro-phenyl)pyrrolidin-3-yl]-ethoxy}-5-trifluoromethyl-pyridine (intermediate XV-B-3) (76 mg, 0.19 mmol) and pyridine (0.03 mL, 0.42 mmol) in CH2Cl2 (1 mL) over 30 minutes. The temperature was raised to RT, and stirring was continued over night. The organic phase was washed with H2O, dried over Na2SO4. Concentration under vacuo yielded and column chromatography (SiO2, EtOAc/H, 1:4) yielded 36 mg (41%) of the title compound as a viscous colorless oil.

Workup

  1. waitwas continued over night
  2. washThe organic phase was washed with H2O
  3. dry with materialdried over Na2SO4
  4. concentrationConcentration under vacuo
  5. customyielded

Sources & evidence

ORD record
ord-14551c44a6eb445c85c9c5847ff0da7d
Source dataset
uspto-grants-2010_10
Patent number
US07812021B2

Reaction notes

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