Benzyl Alcohol → (3-Benzyloxy-5-trifluoromethyl-benzyl)-(5'-isopropyl-2'-methoxy-4-trifluoromethyl-biphenyl-2-ylmethyl)-(5-morpholin-4-yl-pyrimidin-2-yl)-amine

HRID 604156Notes

Reaction equation

HRID 604156 reaction equation
O1CCCC1.[H-].[Na+].[CH2:8]([OH:15])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.F[C:17]1[CH:18]=[C:19]([CH:56]=[C:57]([C:59]([F:62])([F:61])[F:60])[CH:58]=1)[CH2:20][N:21]([CH2:34][C:35]1[CH:40]=[C:39]([C:41]([F:44])([F:43])[F:42])[CH:38]=[CH:37][C:36]=1[C:45]1[CH:50]=[C:49]([CH:51]([CH3:53])[CH3:52])[CH:48]=[CH:47][C:46]=1[O:54][CH3:55])[C:22]1[N:27]=[CH:26][C:25]([N:28]2[CH2:33][CH2:32][O:31][CH2:30][CH2:29]2)=[CH:24][N:23]=1>[Cl-].[Na+].O>[CH2:8]([O:15][C:17]1[CH:18]=[C:19]([CH:56]=[C:57]([C:59]([F:62])([F:60])[F:61])[CH:58]=1)[CH2:20][N:21]([CH2:34][C:35]1[CH:40]=[C:39]([C:41]([F:42])([F:43])[F:44])[CH:38]=[CH:37][C:36]=1[C:45]1[CH:50]=[C:49]([CH:51]([CH3:53])[CH3:52])[CH:48]=[CH:47][C:46]=1[O:54][CH3:55])[C:22]1[N:27]=[CH:26][C:25]([N:28]2[CH2:29][CH2:30][O:31][CH2:32][CH2:33]2)=[CH:24][N:23]=1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1

Participants

6

Reactant 4

HCID 244Benzyl AlcoholHCID 8028Tetrahydrofuran2×HCID 24758Sodium hydrideHCID 86626895HCID 86626895, compound

Product 1

HCID 86626896(3-Benzyloxy-5-trifluoromethyl-benzyl)-(5'-isopropyl-2'-methoxy-4-trifluoromethyl-biphenyl-2-ylmethyl)-(5-morpholin-4-yl-pyrimidin-2-yl)-amine

Reagents, catalysts & solvents 1

HCID 57417360Sodium chloride; waterSolvent

Procedure

To tetrahydrofuran (6 ml) is added sodium hydride (60%) (390 mg) under nitrogen atmosphere, followed by an addition dropwise of benzyl alcohol (1.01 ml) under water-cooling, and the mixture is stirred at the same temperature for 30 minutes. To this reaction mixture is added a mixture of (3-fluoro-5-trifluoromethyl-benzyl)-(5′-isopropyl-2′-methoxy-4-trifluoromethyl-biphenyl-2-ylmethyl)-(5-morpholin-4-yl-pyrimidin-2-yl)-amine (430 mg) and tetrahydrofuran (4 ml) and the mixture is stirred under nitrogen atmosphere at 70° C. overnight. To the reaction solution are added a saturated brine, and the mixture is extracted with ethyl acetate. The organic layer is washed with a saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The resulting residue is purified by NH-silica gel column chromatography (hexane:ethyl acetate=97:3→17:3) to give (3-benzyloxy-5-trifluoromethyl-benzyl)-(5′-isopropyl-2′-methoxy-4-trifluoromethyl-biphenyl-2-ylmethyl)-(5-morpholin-4-yl-pyrimidin-2-yl)-amine (221 mg). MS (m/z): 751 [M+H]+

Workup

  1. temperaturecooling
  2. additionTo this reaction mixture is added
  3. stirringthe mixture is stirred under nitrogen atmosphere at 70° C. overnight
  4. extractionthe mixture is extracted with ethyl acetate
  5. washThe organic layer is washed with a saturated brine
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe resulting residue is purified by NH-silica gel column chromatography (hexane:ethyl acetate=97:3→17:3)

Sources & evidence

ORD record
ord-92b49f757be04f41b92f445246a9e72f
Source dataset
uspto-grants-2011_03
Patent number
US07906517B2

Reaction notes

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