Water → (3,5-Bis-trifluoromethyl-benzyl)-(5-bromo-pyrimidin-2-yl)-(2-fluoro-5-trifluoromethyl-benzyl)-amine

HRID 604065Notes

Reaction equation

HRID 604065 reaction equation
[F:1][C:2]([F:23])([F:22])[C:3]1[CH:4]=[C:5]([CH:15]=[C:16]([C:18]([F:21])([F:20])[F:19])[CH:17]=1)[CH2:6][NH:7][C:8]1[N:13]=[CH:12][C:11]([Br:14])=[CH:10][N:9]=1.[H-].[Na+].Br[CH2:27][C:28]1[CH:33]=[C:32]([C:34]([F:37])([F:36])[F:35])[CH:31]=[CH:30][C:29]=1[F:38].O>CN(C)C=O.C(OCC)(=O)C>[F:23][C:2]([F:1])([F:22])[C:3]1[CH:4]=[C:5]([CH:15]=[C:16]([C:18]([F:21])([F:20])[F:19])[CH:17]=1)[CH2:6][N:7]([C:8]1[N:13]=[CH:12][C:11]([Br:14])=[CH:10][N:9]=1)[CH2:27][C:28]1[CH:33]=[C:32]([C:34]([F:35])([F:37])[F:36])[CH:31]=[CH:30][C:29]=1[F:38]

Participants

7

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 27375712-(Bromomethyl)-1-fluoro-4-(trifluoromethyl)benzeneHCID 57551007(3,5-Bis-trifluoromethyl-benzyl)-(5-bromopyrimidin-2-yl)-amine

Product 1

HCID 86626777(3,5-Bis-trifluoromethyl-benzyl)-(5-bromo-pyrimidin-2-yl)-(2-fluoro-5-trifluoromethyl-benzyl)-amineYield 99%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

(3,5-Bis-trifluoromethyl-benzyl)-(5-bromo-pyrimidin-2-yl)-amine (8.55 g) is dissolved in N,N-dimethylformamide (20 ml), and thereto is added sodium hydride (60%) (855 mg) under ice-cooling, and the mixture is stirred for 15 minutes. To the reaction solution are added 2-bromomethyl-1-fluoro-4-trifluoromethyl-benzene (5 g), and the mixture is stirred at room temperature overnight. To the reaction solution are added water and ethyl acetate, 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 purified by silica gel column chromatography (hexane:ethyl acetate=1:0→9:1) to give (3,5-bis-trifluoromethyl-benzyl)-(5-bromo-pyrimidin-2-yl)-(2-fluoro-5-trifluoromethyl-benzyl)-amine (11.1 g). MS (m/z): 576/578 [M+H]+

Workup

  1. temperaturecooling
  2. stirringthe mixture is stirred at room temperature overnight
  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. customThe resulting residue is purified by silica gel column chromatography (hexane:ethyl acetate=1:0→9:1)

Sources & evidence

ORD record
ord-790eb2838c6c4154b0c594b9c6e27e3c
Source dataset
uspto-grants-2011_03
Patent number
US07906517B2

Reaction notes

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