Hydrochloric Acid → 4-(2-Carboxy-4-cyano-phenyl)-3,6-dimethyl-2-oxo-1-(3-trifluoromethyl-phenyl)-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid ethyl ester

HRID 927006Notes

Reaction equation

HRID 927006 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]=2[C:33]([O:35]C)=[O:34])[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].[OH-].[Li+].O.Cl>O1CCOCC1>[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:33]([OH:35])=[O:34])[N:8]([CH3:24])[C:9](=[O:23])[N:10]([C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([C:19]([F:20])([F:22])[F:21])[CH:14]=2)[C:11]=1[CH3:12])=[O:5])[CH3:2]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 962Water2×HCID 3939Lithium HydroxideHCID 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 ester2×

Product 1

HCID 1186916744-(2-Carboxy-4-cyano-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 312751,4-DioxaneSolvent

Procedure

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 (intermediate 9)(3.39 g, 6.76 mmol) and lithium hydroxide (194.4 mg, 8.11 mmol) are stirred in 1,4-dioxane (84 ml) and water (6.0 mL) at room temperature for 100 h. Water is added and the mixture is acidified with hydrochloric acid (4.0 mol/L) to a pH value of 3. The aqueous phase is extracted with dichloromethane three times. The combined organic phase is dried over MgSO4, concentrated and purified by reversed phase HPLC. Yield: 1.34 g. ESI mass spectrum: [M+H]+=488; Retention time HPLC: 1.08 min (HPLC method Z018_S04).

Workup

  1. extractionThe aqueous phase is extracted with dichloromethane three times
  2. dry with materialThe combined organic phase is dried over MgSO4
  3. concentrationconcentrated
  4. custompurified by reversed phase HPLC
  5. custom1.08 min (HPLC method Z018_S04)

Sources & evidence

ORD record
ord-9e713643fe584da4b1a10c1cac6d9e37
Source dataset
uspto-grants-2016_03
Patent number
US09290457B2

Reaction notes

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