Dichloromethane → 4-(4-Cyano-2-methoxycarbonyl-phenyl)-3,6-dimethyl-2-oxo-1-(3-trifluoromethyl-phenyl)-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid ethyl ester

HRID 927005Notes

Reaction equation

HRID 927005 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[CH:7]([C:25]2[CH:30]=[CH:29][C:28]([C:31]#[N:32])=[CH:27][C:26]=2Br)[N:8]([CH3:24])[C:9](=[O:23])[N:10]([C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([C:19]([F:22])([F:21])[F:20])[CH:14]=2)[C:11]=1[CH3:12])=[O:5])[CH3:2].Cl[CH2:35]Cl.[C:37]([O-:40])(=[O:39])C.[Na+].[C]=O>CO>[CH2:1]([O:3][C:4]([C:6]1[CH:7]([C:25]2[CH:30]=[CH:29][C:28]([C:31]#[N:32])=[CH:27][C:26]=2[C:37]([O:40][CH3:35])=[O:39])[N:8]([CH3:24])[C:9](=[O:23])[N:10]([C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([C:19]([F:22])([F:21])[F:20])[CH:14]=2)[C:11]=1[CH3:12])=[O:5])[CH3:2]

Participants

6

Reactant 4

HCID 6344Dichloromethane2×HCID 517045Sodium AcetateHCID 118691682HCID 118691682, compound2×HCID 178418416HCID 178418416, compound

Product 1

HCID 1186916664-(4-Cyano-2-methoxycarbonyl-phenyl)-3,6-dimethyl-2-oxo-1-(3-trifluoromethyl-phenyl)-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

4-(2-Bromo-4-cyano-phenyl)-3,6-dimethyl-2-oxo-1-(3-trifluoromethyl-phenyl)-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid ethyl ester (intermediate 8, 7.16 g, 13.7 mmol), 1.1-bis(diphenylphosphino)-ferrocendichloropalladium(H), complex with dichloromethane (1:1) (559.3 mg, 0.69 mmol) and sodium acetate (3.37 g, 41.1 mmol) are suspended in methanol (120 mL) and treated with carbon monoxide at 8 bar and 100° C. for 19 h. A small amount of 1.1-bis(diphenylphosphino)-ferrocendichloropalladium(II), complex with dichloromethane (1:1) is added and the reaction under carbon monoxide is continued at 8 bar and 100° C. for 19 h. The reaction mixture is concentrated and purified by reversed phase HPLC. Yield: 3.70 g. ESI mass spectrum: [M+H]+=502; Retention time HPLC: 1.20 min (HPLC method Z018_S04)

Workup

  1. customthe reaction under carbon monoxide
  2. concentrationThe reaction mixture is concentrated
  3. custompurified by reversed phase HPLC
  4. custom1.20 min (HPLC method Z018_S04)

Sources & evidence

ORD record
ord-4d3e3140e07742639a434e53440bcb6c
Source dataset
uspto-grants-2016_03
Patent number
US09290457B2

Reaction notes

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