Water → Tert-butyl 4-{2-[(3,5-bis-trifluoromethyl-benzyl)-(2-bromo-5-methoxy-4-trifluoromethyl-benzyl)-amino]-pyrimidin-5-yloxy}-butyrate

HRID 604174Notes

Reaction equation

HRID 604174 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][NH:7][C:8]1[N:13]=[CH:12][C:11]([O:14][CH2:15][CH2:16][CH2:17][C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])=[CH:10][N:9]=1.[H-].[Na+].[Br:36][C:37]1[CH:42]=[C:41]([C:43]([F:46])([F:45])[F:44])[C:40]([O:47][CH3:48])=[CH:39][C:38]=1[CH2:49]Br.O>CN(C)C=O.C(OCC)(=O)C>[F:33][C:2]([F:1])([F:32])[C:3]1[CH:4]=[C:5]([CH:25]=[C:26]([C:28]([F:29])([F:30])[F:31])[CH:27]=1)[CH2:6][N:7]([CH2:49][C:38]1[CH:39]=[C:40]([O:47][CH3:48])[C:41]([C:43]([F:44])([F:46])[F:45])=[CH:42][C:37]=1[Br:36])[C:8]1[N:9]=[CH:10][C:11]([O:14][CH2:15][CH2:16][CH2:17][C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])=[CH:12][N:13]=1

Participants

7

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 666026811-Bromo-2-bromomethyl-4-methoxy-5-trifluoromethyl-benzeneHCID 86626523Tert-butyl 4-[2-(3,5-bis-trifluoromethyl-benzylamino)-pyrimidin-5-yloxy]-butyrate

Product 1

HCID 86626907Tert-butyl 4-{2-[(3,5-bis-trifluoromethyl-benzyl)-(2-bromo-5-methoxy-4-trifluoromethyl-benzyl)-amino]-pyrimidin-5-yloxy}-butyrateYield 54.8%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Tert-butyl 4-[2-(3,5-bis-trifluoromethyl-benzylamino)-pyrimidin-5-yloxy]-butyrate (300 mg) is dissolved in N,N-dimethylformamide (4 ml) and thereto is added sodium hydride (60%) (33 mg) under ice-cooling, and the mixture is stirred for 15 minutes and thereto is added 1-bromo-2-bromomethyl-4-methoxy-5-trifluoromethyl-benzene (327 mg) and the mixture is stirred at room temperature overnight. Thereto 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=19:1→17:3) to give tert-butyl 4-{2-[(3,5-bis-trifluoromethyl-benzyl)-(2-bromo-5-methoxy-4-trifluoromethyl-benzyl)-amino]-pyrimidin-5-yloxy}-butyrate (256 mg). MS (m/z): 746/748 [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=19:1→17:3)

Sources & evidence

ORD record
ord-d02b17a1224f44b18440db83db9492ba
Source dataset
uspto-grants-2011_03
Patent number
US07906517B2

Reaction notes

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