Sodium Carbonate → 2-Methyl-5-nitro-4-(4-phenyl-piperidin-1-yl)-6-(2,2,2-trifluoro-ethoxy)-pyrimidine

HRID 1838133Notes

Reaction equation

HRID 1838133 reaction equation
FC(F)(F)S([O:6][CH2:7][C:8]([F:11])([F:10])[F:9])(=O)=O.[CH3:14][C:15]1[NH:20][C:19](=O)[C:18]([N+:22]([O-:24])=[O:23])=[C:17]([N:25]2[CH2:30][CH2:29][CH:28]([C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)[CH2:27][CH2:26]2)[N:16]=1.C(=O)([O-])[O-].[Na+].[Na+].C(=O)([O-])[O-].[K+].[K+]>CC(C)=O>[CH3:14][C:15]1[N:16]=[C:17]([N:25]2[CH2:30][CH2:29][CH:28]([C:31]3[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=3)[CH2:27][CH2:26]2)[C:18]([N+:22]([O-:24])=[O:23])=[C:19]([O:6][CH2:7][C:8]([F:11])([F:10])[F:9])[N:20]=1

Participants

6

Reactant 4

HCID 10340Sodium CarbonateHCID 11430Potassium CarbonateHCID 803662,2,2-Trifluoroethyl trifluoromethanesulfonate2×HCID 135617199HCID 135617199, compound

Product 1

HCID 187532372-Methyl-5-nitro-4-(4-phenyl-piperidin-1-yl)-6-(2,2,2-trifluoro-ethoxy)-pyrimidineYield 30.5%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

0.591 g (2.55 mmol) of 2,2,2-trifluoroethyl trifluoromethanesulfonate were added slowly at room temperature to a suspension of 0.200 g (0.636 mmol) of the 2-methyl-5-nitro-6-(4-phenyl-piperidin-1-yl)-3H-pyrimidin-4-one (example 5) and 0.135 g (1.27 mmol) of sodium carbonate in 5.0 ml of acetone. After stirring of the reaction mixture for 2 hours, 0.136 g (0.99 mmol) of potassium carbonate were added and stirring continued for 18 hours. Additional 0.296 g (1.27 mmol) of 2,2,2-trifluoroethyl trifluoromethanesulfonate were added and stirring continued for 4 hours. The reaction mixture was then poured into 50 ml of an ice/water mixture and extracted 3 times with 50 ml of dichloromethane. The combined dichloromethane phases were dried over magnesium sulfate and evaporated under reduced pressure. The residue formed was chromatographed on silica gel with a 9:1 to 1:1 v/v gradient of hexane and ethylacetate as the eluent giving 0.077 g (0.194 mmol, 30.5% of theory) of the 2-methyl-5-nitro-4-(4-phenyl-piperidin-1-yl)-6-(2,2,2-trifluoro-ethoxy)-pyrimidine as a light yellow solid; m.p. 114-117° C.; MS: [M+H]+=397; and 0.166 g (0.419 mmol, 65.8% of theory) of the 2-methyl-5-nitro-6-(4-phenyl-piperidin-1-yl)-3-(2,2,2-trifluoro-ethyl)-3H-pyrimidin-4-one as yellowish solid;

Workup

  1. stirringstirring
  2. waitcontinued for 18 hours
  3. stirringstirring
  4. waitcontinued for 4 hours
  5. extractionextracted 3 times with 50 ml of dichloromethane
  6. dry with materialThe combined dichloromethane phases were dried over magnesium sulfate
  7. customevaporated under reduced pressure
  8. customThe residue formed
  9. customwas chromatographed on silica gel with a 9:1 to 1:1 v/v gradient of hexane and ethylacetate as the eluent

Sources & evidence

ORD record
ord-e979c4b34541418d9be247a7f3f78035
Source dataset
uspto-grants-2004_01
Patent number
US06673795B2

Reaction notes

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