Sodium hydride → HCID 117899568, compound

HRID 522270Notes

Reaction equation

HRID 522270 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][OH:15])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[Br:18][C:19]1[CH:24]=[CH:23][C:22]([CH2:25]Br)=[C:21]([C:27]([F:30])([F:29])[F:28])[CH:20]=1.[Cl-].[NH4+]>CN(C=O)C.CCOC(C)=O>[Br:18][C:19]1[CH:24]=[CH:23][C:22]([CH2:25][O:15][CH2:14][CH:11]2[CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH2:9][CH2:10]2)=[C:21]([C:27]([F:28])([F:29])[F:30])[CH:20]=1

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 2764081Tert-butyl 4-(hydroxymethyl)piperidine-1-carboxylateHCID 534180314-Bromo-1-(bromomethyl)-2-(trifluoromethyl)benzene

Product 1

HCID 117899568HCID 117899568, compoundYield 76.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

1-(tert-Butoxycarbonyl)-4-piperidinemethanol (400 mg) was added to a mixture of 60% sodium hydride (90 mg) and DMF (11 mL) under ice-cooling in a nitrogen atmosphere, and the mixture was stirred for 10 minutes. A solution of 4-bromo-1-(bromomethyl)-2-(trifluoromethyl)benzene (550 mg) in DMF (2 mL) was added to the mixture under ice-cooling. After the reaction mixture was stirred for 30 minutes under ice-cooling, the temperature of the reaction mixture was raised to room temperature, and stirring was performed for 30 minutes. After a saturated aqueous ammonium chloride solution was added to the reaction mixture, extraction thereof was performed using an EtOAc-Hex mixed solvent (1:1), and the extract was washed with water and saturated brine. The organic layer was dried over MgSO4 and filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (Hex:EtOAc=99:1 to 90:10), whereby tert-butyl 4-({[4-bromo-2-(trifluoromethyl)benzyl]oxy}methyl)piperidine-1-carboxylate (598 mg) was obtained as a pale yellow oil.

Workup

  1. temperaturecooling in a nitrogen atmosphere
  2. temperaturecooling
  3. stirringAfter the reaction mixture was stirred for 30 minutes under ice-
  4. temperaturecooling
  5. stirringstirring
  6. waitwas performed for 30 minutes
  7. additionmixed solvent (1:1)
  8. washthe extract was washed with water and saturated brine
  9. dry with materialThe organic layer was dried over MgSO4
  10. filtrationfiltered
  11. concentrationthe filtrate was concentrated under reduced pressure
  12. customThe residue was purified by silica gel column chromatography (Hex:EtOAc=99:1 to 90:10)

Sources & evidence

ORD record
ord-8240e50a41ab40819007fdbb48da7577
Source dataset
uspto-grants-2016_05
Patent number
US09328118B2

Reaction notes

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