Triethylamine → (3SR,4RS)-3-(3,4-Dichloro-phenyl)-4-[(3-fluoro-4-trifluoromethyl-benzyl)-methyl-amino]-pyrrolidine-1-carboxylic acid 3-chloro-propyl ester

HRID 910463Notes

Reaction equation

HRID 910463 reaction equation
Cl[C:2]([O:4][CH2:5][CH2:6][CH2:7][Cl:8])=[O:3].[Cl:9][C:10]1[CH:11]=[C:12]([CH:17]2[CH2:21][NH:20][CH2:19][CH:18]2[N:22]([CH2:24][C:25]2[CH:30]=[CH:29][C:28]([C:31]([F:34])([F:33])[F:32])=[C:27]([F:35])[CH:26]=2)[CH3:23])[CH:13]=[CH:14][C:15]=1[Cl:16].C(N(CC)CC)C>C1COCC1>[Cl:8][CH2:7][CH2:6][CH2:5][O:4][C:2]([N:20]1[CH2:19][CH:18]([N:22]([CH2:24][C:25]2[CH:30]=[CH:29][C:28]([C:31]([F:34])([F:32])[F:33])=[C:27]([F:35])[CH:26]=2)[CH3:23])[CH:17]([C:12]2[CH:13]=[CH:14][C:15]([Cl:16])=[C:10]([Cl:9])[CH:11]=2)[CH2:21]1)=[O:3]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 69399Carbonochloridic acid, 3-chloropropyl esterHCID 75231672[(3RS,4SR)-4-(3,4-Dichloro-phenyl)-pyrrolidin-3-yl]-(3-fluoro-4-trifluoromethyl-benzyl)-methyl-amine

Product 1

HCID 72253477(3SR,4RS)-3-(3,4-Dichloro-phenyl)-4-[(3-fluoro-4-trifluoromethyl-benzyl)-methyl-amino]-pyrrolidine-1-carboxylic acid 3-chloro-propyl esterYield 104.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirred solution of 3-chloropropyl chloroformate (0.058 ml, 0.47 mmol) in THF (5 ml) at RT was added over 1 hour a solution of [(3RS,4SR)-4-(3,4-Dichloro-phenyl)-pyrrolidin-3-yl]-(3-fluoro-4-trifluoromethyl-benzyl)-methyl-amine (Intermediate VIII-1, 0.187 g, 0.44 mmol) and triethyl amine (0.068 ml, 0.48 mmol) in THF (2 mL). The reaction was stirred over night, quenched by addition of an aqueous solution of NaHCO3, and the product extracted with EtOAC. The organic phases were concentrated under vacuo to yielded 0.25 g (99%) of the title compound as a light yellow oil. The product was used in the next steps without further purification. ES-MS m/e: 542.7 (M+H+).

Workup

  1. customquenched by addition of an aqueous solution of NaHCO3
  2. extractionthe product extracted with EtOAC
  3. concentrationThe organic phases were concentrated under vacuo

Sources & evidence

ORD record
ord-2f0326c7581148d0b42f0495f525e918
Source dataset
uspto-grants-2011_09
Patent number
US08022099B2

Reaction notes

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