Potassium Carbonate → Proline benzyl ester

HRID 2265992Notes

Reaction equation

HRID 2265992 reaction equation
Cl.[CH2:2]([O:9][C:10](=[O:16])[C@@H:11]1[CH2:15][CH2:14][CH2:13][NH:12]1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.CCOC(C)=O>[CH2:2]([O:9][C:10]([CH:11]1[CH2:15][CH2:14][CH2:13][NH:12]1)=[O:16])[C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=1

Participants

5

Reactant 2

HCID 11430Potassium CarbonateHCID 2733413Proline benzyl ester hydrochloride

Product 1

HCID 99767Proline benzyl esterYield 55.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

L-Proline benzyl ester hydrochloride (96 mg, 2.0 eq) in DMF was put into a flask and K2CO3 (132 mg, 2.0 eq) was added, stirred for a while, and 3-(2-chloro-6-trifluoromethyl-4-yl-pyridin-3-yl)-acrylic acid (50 mg) was added at room temperature. The reaction mixture was stirred for 18 hrs. After the reaction was completed through the TLC checking, the mixture was diluted with EtOAc, washed with 1N HCl solution. The organic layer was dried over anhydrous MgSO4 and concentrated under reduced pressure to give a crude 6-trifluoromethyl-pyridin-2-yl}-pyrrolidin-2-yl carboxylic acid benzyl ester (45 mg). N-(4-Aminomethyl-5-ethynyl-2-fluoro-phenyl)-methanesulfonamide, HCl salt (30 mg, 0.11 mmol) was reacted with 6-trifluoromethyl-pyridin-2-yl}-pyrrolidin-2-yl-carboxylic acid benzyl ester (45 mg) to give 1-{3-[2-(3-ethynyl-5-fluoro-4-methanesulfonylamino-benzylcarbamoyl)-vinyl]-6-trifluoromethyl-pyridin-2-yl}-pyrrolidin-2-yl-carboxylic acid benzyl ester (3.2 mg, 4.5%) after purification by column chromatography (EtOAc/MeOH=10/1).

Workup

  1. additionwas added at room temperature
  2. washwashed with 1N HCl solution
  3. dry with materialThe organic layer was dried over anhydrous MgSO4
  4. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-9b472926bfcd4772ae483234a5e258dc
Source dataset
uspto-grants-2010_12
Patent number
US07858621B2

Reaction notes

Loading…