Ethyl Acetate → 2-[(2-Benzyloxy-5-trifluoromethyl-benzyl)-(3,5-bis-trifluoromethyl-benzyl)-amino]-pyrimidin-5-ol

HRID 604067Notes

Reaction equation

HRID 604067 reaction equation
[CH2:1]([O:8][C:9]1[CH:38]=[CH:37][C:36]([C:39]([F:42])([F:41])[F:40])=[CH:35][C:10]=1[CH2:11][N:12]([CH2:20][C:21]1[CH:26]=[C:25]([C:27]([F:30])([F:29])[F:28])[CH:24]=[C:23]([C:31]([F:34])([F:33])[F:32])[CH:22]=1)[C:13]1[N:18]=[CH:17][C:16](Br)=[CH:15][N:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([O-])(=[O:45])C.[K+].B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.C(OCC)(=O)C>CS(C)=O.[Cl-].[Na+].O>[CH2:1]([O:8][C:9]1[CH:38]=[CH:37][C:36]([C:39]([F:42])([F:41])[F:40])=[CH:35][C:10]=1[CH2:11][N:12]([CH2:20][C:21]1[CH:26]=[C:25]([C:27]([F:30])([F:29])[F:28])[CH:24]=[C:23]([C:31]([F:34])([F:33])[F:32])[CH:22]=1)[C:13]1[N:18]=[CH:17][C:16]([OH:45])=[CH:15][N:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 86626822(2-Benzyloxy-5-trifluoromethyl-benzyl)-(3,5-bis-trifluoromethyl-benzyl)-(5-bromo-pyrimidin-2-yl)-amine

Product 1

HCID 866268232-[(2-Benzyloxy-5-trifluoromethyl-benzyl)-(3,5-bis-trifluoromethyl-benzyl)-amino]-pyrimidin-5-olYield 65.8%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
80 °C

Procedure

(2-Benzyloxy-5-trifluoromethyl-benzyl)-(3,5-bis-trifluoromethyl-benzyl)-(5-bromo-pyrimidin-2-yl)-amine (12.9 g) is dissolved in dimethylsulfoxide (150 ml), and thereto are added [1,1-bis(diphenylphosphino)ferrocene]dichloropalladium dichloromethane complex (3.17 g), potassium acetate (5.71 g) and bis(pinacolato)diboron (9.85 g), and the mixture is heated to 80° C. under nitrogen atmosphere for 1 hour and 30 minutes. The reaction solution is cooled to room temperature, and thereto are added a saturated brine and ethyl acetate, and the mixture is separated, dried over magnesium sulfate, and concentrated under reduced pressure. The resulting residue is dissolved in tetrahydrofuran (150 ml), and thereto is added dropwise a 30% aqueous hydrogen peroxide solution (40 ml) under ice-cooling. Two hours thereafter, thereto is added a saturated aqueous sodium thiosulfate solution to consume the excess hydrogen peroxide, and thereto is added 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 (hexane:ethyl acetate=9:1 to 7:3) to give 2-[(2-benzyloxy-5-trifluoromethyl-benzyl)-(3,5-bis-trifluoromethyl-benzyl)-amino]-pyrimidin-5-ol (7.68 g). MS (m/z): 602 [M+H]+

Workup

  1. temperatureThe reaction solution is cooled to room temperature
  2. customthe mixture is separated
  3. dry with materialdried over magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. dissolutionThe resulting residue is dissolved in tetrahydrofuran (150 ml)
  6. additionis added dropwise a 30% aqueous hydrogen peroxide solution (40 ml) under ice-
  7. temperaturecooling
  8. additionTwo hours thereafter, thereto is added a saturated aqueous sodium thiosulfate solution
  9. customto consume the excess hydrogen peroxide
  10. additionis added ethyl acetate
  11. customthe mixture is separated
  12. washThe organic layer is washed with a saturated brine
  13. dry with materialdried over magnesium sulfate
  14. concentrationconcentrated under reduced pressure
  15. customThe resulting residue is purified by silica gel column chromatography (hexane:ethyl acetate=9:1 to 7:3)

Sources & evidence

ORD record
ord-84a679ee473f44c4976f0bab6447b5d9
Source dataset
uspto-grants-2011_03
Patent number
US07906517B2

Reaction notes

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