Triethylamine → Benzyl 2-(3-fluoro-4-(methoxycarbonyl)phenyl)pyrrolidine-1-carboxylate

HRID 415154Notes

Reaction equation

HRID 415154 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:12][CH2:11][CH2:10][N:9]2[C:13]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[O:14])=[CH:4][C:3]=1[F:23].C(N(CC)CC)C.[C]=O>CO.[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[F:23][C:3]1[CH:4]=[C:5]([CH:8]2[CH2:12][CH2:11][CH2:10][N:9]2[C:13]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[O:14])[CH:6]=[CH:7][C:2]=1[C:13]([O:15][CH3:16])=[O:14]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 66620873Benzyl 2-(4-bromo-3-fluorophenyl)pyrrolidine-1-carboxylateHCID 178418416HCID 178418416, compound

Product 1

HCID 66621283Benzyl 2-(3-fluoro-4-(methoxycarbonyl)phenyl)pyrrolidine-1-carboxylateYield 120.1%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 887MethanolSolvent

Procedure

A mixture of benzyl 2-(4-bromo-3-fluorophenyl)pyrrolidine-1-carboxylate (15.3 g, 40.6 mmol), 1,1′-bis(diphenylphosphino)ferrocene palladium (II) dichloride (1.67 g, 2.0 mmol) and triethylamine (8.4 mL, 60.9 mmol) in methanol (180 mL) was stirred under 60 psi of carbon monoxide at 100° C. for 4 hour. After cooling to ambient temperature, the mixture was concentrated and the residue purified by flash chromatograph on silica gel using a gradient of 8-15% ethyl acetate in petroleum ether to give benzyl 2-(3-fluoro-4-(methoxycarbonyl)phenyl)pyrrolidine-1-carboxylate as colorless oil (8.71 g, yield 60%). LC-MS (ESI) m/z: 358 (M+1)+.

Workup

  1. concentrationthe mixture was concentrated
  2. customthe residue purified by flash chromatograph on silica gel using a gradient of 8-15% ethyl acetate in petroleum ether

Sources & evidence

ORD record
ord-c220e25a994d417eabcd62dcbabc6b30
Source dataset
uspto-grants-2012_01
Patent number
US08088760B2

Reaction notes

Loading…