Water → Benzyl (3,5-bis-trifluoromethyl-benzyl)-(5-hydroxy-pyrimidin-2-yl)-carbamate

HRID 604205Notes

Reaction equation

HRID 604205 reaction equation
[F:1][C:2]([F:33])([F:32])[C:3]1[CH:4]=[C:5]([CH:25]=[C:26]([C:28]([F:31])([F:30])[F:29])[CH:27]=1)[CH2:6][N:7]([C:18]1[N:23]=[CH:22][C:21](Br)=[CH:20][N:19]=1)[C:8](=[O:17])[O:9][CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.C([O-])(=[O:36])C.[K+].B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.O>CS(C)=O.C(OCC)(=O)C>[F:1][C:2]([F:33])([F:32])[C:3]1[CH:4]=[C:5]([CH:25]=[C:26]([C:28]([F:31])([F:30])[F:29])[CH:27]=1)[CH2:6][N:7]([C:18]1[N:23]=[CH:22][C:21]([OH:36])=[CH:20][N:19]=1)[C:8](=[O:17])[O:9][CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1

Participants

7

Reactant 4

HCID 962WaterHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 86626518Benzyl (3,5-bis-trifluoromethyl-benzyl)-(5-bromo-pyrimidin-2-yl)-carbamate

Product 1

HCID 86626519Benzyl (3,5-bis-trifluoromethyl-benzyl)-(5-hydroxy-pyrimidin-2-yl)-carbamateYield 95.6%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

Benzyl (3,5-bis-trifluoromethyl-benzyl)-(5-bromo-pyrimidin-2-yl)-carbamate (11.5 g), [1,1′-bis(diphenylphosphino)ferrocene]-dichloropalladium dichloromethane complex (3.51 g), potassium acetate (6.33 g) and bis(pinacolato)diboron (10.9 g) are dissolved in dimethylsulfoxide (75 ml), and the mixture is heated to 80° C. under nitrogen atmosphere and stirred for 30 minutes. The reaction solution is cooled to room temperature and thereto are added water and ethyl acetate, and the insoluble materials are removed by filtration through Celite™, and the mixture is separated and the organic layer is washed with a saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The resulting residue is dissolved in tetrahydrofuran (100 ml) and thereto is added dropwise a 30% aqueous hydrogen peroxide solution (50 ml) under ice-cooling and the mixture is stirred for 1 hour. Thereto is added a saturated aqueous sodium thiosulfate solution under ice-cooling to consume the excess hydrogen peroxide, followed by an addition of water and ethyl acetate, and the mixture is separated. The organic layer is washed with a saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The resulting residue is purified by silica gel column chromatography (chloroform:methanol=1:0→9:1) to give benzyl (3,5-bis-trifluoromethyl-benzyl)-(5-hydroxy-pyrimidin-2-yl)-carbamate (9.70 g). MS (m/z): 472 [M+H]+

Workup

  1. temperatureThe reaction solution is cooled to room temperature
  2. customthe insoluble materials are removed by filtration through Celite™
  3. customthe mixture is separated
  4. washthe organic layer is washed with a saturated brine
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. dissolutionThe resulting residue is dissolved in tetrahydrofuran (100 ml)
  8. additionis added dropwise a 30% aqueous hydrogen peroxide solution (50 ml) under ice-
  9. temperaturecooling
  10. stirringthe mixture is stirred for 1 hour
  11. additionThereto is added a saturated aqueous sodium thiosulfate solution under ice-
  12. temperaturecooling
  13. customto consume the excess hydrogen peroxide
  14. additionfollowed by an addition of water and ethyl acetate
  15. customthe mixture is separated
  16. washThe organic layer is washed with a saturated brine
  17. dry with materialdried over magnesium sulfate
  18. concentrationconcentrated under reduced pressure
  19. customThe resulting residue is purified by silica gel column chromatography (chloroform:methanol=1:0→9:1)

Sources & evidence

ORD record
ord-c1fb1ab13fc94519ba235159544d827f
Source dataset
uspto-grants-2011_03
Patent number
US07906517B2

Reaction notes

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