Sodium hydride → 1-{4-[({5-[2-Fluoro-3-(hydroxymethyl)phenyl]pyrimidin-2-yl}oxy)methyl]piperidin-1-yl}ethan-1-one

HRID 1021275Notes

Reaction equation

HRID 1021275 reaction equation
[OH:1][CH2:2][CH:3]1[CH2:8][CH2:7][N:6]([C:9](=[O:11])[CH3:10])[CH2:5][CH2:4]1.[H-].[Na+].[Si]([O:21][CH2:22][C:23]1[C:24]([F:36])=[C:25]([C:29]2[CH:30]=[N:31][C:32](Cl)=[N:33][CH:34]=2)[CH:26]=[CH:27][CH:28]=1)(C(C)(C)C)(C)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-].C1COCC1>CCOC(C)=O.O.C1COCC1>[F:36][C:24]1[C:23]([CH2:22][OH:21])=[CH:28][CH:27]=[CH:26][C:25]=1[C:29]1[CH:34]=[N:33][C:32]([O:1][CH2:2][CH:3]2[CH2:4][CH2:5][N:6]([C:9](=[O:11])[CH3:10])[CH2:7][CH2:8]2)=[N:31][CH:30]=1

Participants

8

Reactant 4

HCID 24758Sodium hydrideHCID 11078149TBAF tetrahydrofuranHCID 189349231-[4-(Hydroxymethyl)piperidin-1-yl]ethan-1-oneHCID 866862315-[3-({[tert-Butyl(dimethyl)silyl]oxy}methyl)-2-fluorophenyl]-2-chloropyrimidine

Product 1

HCID 683098421-{4-[({5-[2-Fluoro-3-(hydroxymethyl)phenyl]pyrimidin-2-yl}oxy)methyl]piperidin-1-yl}ethan-1-oneYield 82%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

1-[4-(Hydroxymethyl)piperidin-1-yl]ethan-1-one (200 mg) and THF (4 ml) were mixed, and NaH (70 mg) was added thereto, followed by stirring at room temperature for minutes. 5-[3-({[tert-Butyl(dimethyl)silyl]oxy}methyl)-2-fluorophenyl]-2-chloropyrimidine (200 mg) was added to the reaction mixture, followed by stirring at room temperature for 1 hour, and then 1 M TBAF/THF (1.2 ml) was added thereto, followed by stirring at room temperature. Water and EtOAc were added to the reaction mixture, and the organic layer was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane/EtOAc/CHCl3/MeOH) to obtain 1-{4-[({5-[2-fluoro-3-(hydroxymethyl)phenyl]pyrimidin-2-yl}oxy)methyl]piperidin-1-yl}ethan-1-one (167 mg).

Workup

  1. stirringby stirring at room temperature for 1 hour
  2. stirringby stirring at room temperature
  3. concentrationthe organic layer was concentrated under reduced pressure
  4. customThe obtained residue was purified by silica gel column chromatography (hexane/EtOAc/CHCl3/MeOH)

Sources & evidence

ORD record
ord-fea6a9409b87460aab500140e1aed2fa
Source dataset
uspto-grants-2014_05
Patent number
US08716470B2

Reaction notes

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