Water → HCID 86626917, compound

HRID 604187Notes

Reaction equation

HRID 604187 reaction equation
[OH:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]([CH2:31][C:32]2[CH:33]=[C:34]([CH:37]=[C:38]([C:40]([F:43])([F:42])[F:41])[CH:39]=2)[C:35]#[N:36])[CH2:9][C:10]2[CH:15]=[C:14]([C:16]([F:19])([F:18])[F:17])[CH:13]=[CH:12][C:11]=2[C:20]2[CH:25]=[C:24]([CH:26]([CH3:28])[CH3:27])[CH:23]=[CH:22][C:21]=2[O:29][CH3:30])=[N:6][CH:7]=1.[H-].[Na+].Br[CH2:47][CH2:48][CH2:49][C:50]([O:52][C:53]([CH3:56])([CH3:55])[CH3:54])=[O:51].O>CN(C)C=O>[C:35]([C:34]1[CH:33]=[C:32]([CH:39]=[C:38]([C:40]([F:43])([F:41])[F:42])[CH:37]=1)[CH2:31][N:8]([CH2:9][C:10]1[CH:15]=[C:14]([C:16]([F:18])([F:19])[F:17])[CH:13]=[CH:12][C:11]=1[C:20]1[CH:25]=[C:24]([CH:26]([CH3:28])[CH3:27])[CH:23]=[CH:22][C:21]=1[O:29][CH3:30])[C:5]1[N:6]=[CH:7][C:2]([O:1][CH2:47][CH2:48][CH2:49][C:50]([O:52][C:53]([CH3:56])([CH3:55])[CH3:54])=[O:51])=[CH:3][CH:4]=1)#[N:36]

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 2757253tert-Butyl 4-bromobutanoateHCID 86626918HCID 86626918, compound

Product 1

HCID 86626917HCID 86626917, compoundYield 91.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

3-{[(5-Hydroxy-pyridin-2-yl)-(5′-isopropyl-2′-methoxy-4-trifluoromethyl-biphenyl-2-ylmethyl)-amino]-methyl}-5-trifluoromethyl-benzonitrile (150 mg) is dissolved in N,N-dimethylformamide (2.5 ml), and thereto is added 60% sodium hydride (12 mg) under ice-cooling and the mixture is stirred for 30 minutes and thereto is added tert-butyl 4-bromobutyrate (85 mg), and the mixture is stirred at room temperature for 6 hours. To the reaction solution is added water under ice-cooling, and the mixture is extracted with methylene chloride, and the organic layer is washed with a saturated brine, and the mixture is dried over magnesium sulfate and is concentrated under reduced pressure. The resulting residue is purified by silica gel column chromatography (hexane:ethyl acetate=9:1→3:1) to give tert-butyl 4-{6-[(3-cyano-5-trifluoromethyl-benzyl)-(5′-isopropyl-2′-methoxy-4-trifluoromethyl-biphenyl-2-ylmethyl)-amino]-pyridin-3-yloxy}-butyrate (169 mg). MS (m/z): 742 [M+H]+

Workup

  1. temperaturecooling
  2. stirringthe mixture is stirred at room temperature for 6 hours
  3. temperaturecooling
  4. extractionthe mixture is extracted with methylene chloride
  5. washthe organic layer is washed with a saturated brine
  6. dry with materialthe mixture is dried over magnesium sulfate
  7. concentrationis concentrated under reduced pressure
  8. customThe resulting residue is purified by silica gel column chromatography (hexane:ethyl acetate=9:1→3:1)

Sources & evidence

ORD record
ord-d36bad7200af433d9a91dc4df3dcdd73
Source dataset
uspto-grants-2011_03
Patent number
US07906517B2

Reaction notes

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