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

HRID 2171674노트

반응식

HRID 2171674 반응식
[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

참가 물질

8

반응물 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

생성물 1

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

시약·촉매·용매 3

HCID 962Water용매HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매

실험 절차

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 10 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 1M 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}e than-1-one (167 mg).

후처리

  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)

출처 및 근거

ORD 기록
ord-6e4591bf49544d56a4ad9596b22faad0
출처 데이터셋
uspto-grants-2015_06
특허 번호
US09051283B2

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