Water → HCID 86626913, compound

HRID 604182Notes

Reaction equation

HRID 604182 reaction equation
[F:1][C:2]([F:45])([F:44])[C:3]1[CH:4]=[C:5]([CH:37]=[C:38]([C:40]([F:43])([F:42])[F:41])[CH:39]=1)[CH2:6][N:7]([C:30]1[CH:35]=[CH:34][C:33](Br)=[CH:32][N:31]=1)[CH2:8][C:9]1[CH:14]=[C:13]([C:15]([F:18])([F:17])[F:16])[CH:12]=[CH:11][C:10]=1[C:19]1[CH:24]=[C:23]([CH:25]([CH3:27])[CH3:26])[CH:22]=[CH:21][C:20]=1[O:28][CH3:29].C([O-])(=O)C.[K+].B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.[OH2:69]>CS(C)=O.C(OCC)(=O)C>[F:45][C:2]([F:1])([F:44])[C:3]1[CH:4]=[C:5]([CH:37]=[C:38]([C:40]([F:43])([F:41])[F:42])[CH:39]=1)[CH2:6][N:7]([CH2:8][C:9]1[CH:14]=[C:13]([C:15]([F:18])([F:17])[F:16])[CH:12]=[CH:11][C:10]=1[C:19]1[CH:24]=[C:23]([CH:25]([CH3:26])[CH3:27])[CH:22]=[CH:21][C:20]=1[O:28][CH3:29])[C:30]1[N:31]=[CH:32][C:33]([OH:69])=[CH:34][CH:35]=1

Participants

7

Reactant 4

HCID 962WaterHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 86626914HCID 86626914, compound

Product 1

HCID 86626913HCID 86626913, compound

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

(3,5-Bis-trifluoromethyl-benzyl)-(5-bromo-pyridin-2-yl)-(5′-isopropyl-2′-methoxy-4-trifluoromethyl-biphenyl-2-ylmethyl)-amine (475 mg), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium methylene chloride complex (55 mg), potassium acetate (198 mg) and bis(pinacolato)diboron (256 mg) are dissolved in dimethylsulfoxide (2 ml), and the mixture is heated to 80° C. under nitrogen atmosphere and stirred for 1 hour. The reaction solution is cooled to room temperature and thereto are added water and ethyl acetate, and the mixture is separated, and the organic layer is washed twice with a saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The resulting residue is dissolved in tetrahydrofuran (10 ml), and thereto is added dropwise a 30% aqueous hydrogen peroxide solution (0.75 ml) under ice-cooling. The reaction solution is stirred at room temperature overnight, and 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 diethylether, and the mixture is separated. The organic layer is washed successively with water and 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=19:1→4:1) to give 6-[(3,5-bis-trifluoromethyl-benzyl)-(5′-isopropyl-2′-methoxy-4-trifluoromethyl-biphenyl-2-ylmethyl)-amino]-pyridin-3-ol (141 mg). MS (m/z): 643 [M+H]+

Workup

  1. temperatureThe reaction solution is cooled to room temperature
  2. customthe mixture is separated
  3. washthe organic layer is washed twice with a saturated brine
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. dissolutionThe resulting residue is dissolved in tetrahydrofuran (10 ml)
  7. additionis added dropwise a 30% aqueous hydrogen peroxide solution (0.75 ml) under ice-
  8. temperaturecooling
  9. stirringThe reaction solution is stirred at room temperature overnight
  10. additionis added a saturated aqueous sodium thiosulfate solution under ice-
  11. temperaturecooling
  12. customto consume the excess hydrogen peroxide
  13. additionfollowed by an addition of water and diethylether
  14. customthe mixture is separated
  15. washThe organic layer is washed successively with water
  16. dry with materiala saturated brine, dried over magnesium sulfate
  17. concentrationconcentrated under reduced pressure
  18. customThe resulting residue is purified by silica gel column chromatography (hexane:ethyl acetate=19:1→4:1)

Sources & evidence

ORD record
ord-9e24ef2083a4418391c3375c516dbae3
Source dataset
uspto-grants-2011_03
Patent number
US07906517B2

Reaction notes

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