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

HRID 2171674ノート

反応式

HRID 2171674 の反応式
[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

参加物

8

反応物 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

生成物 1

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

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-6e4591bf49544d56a4ad9596b22faad0
出典データセット
uspto-grants-2015_06
特許番号
US09051283B2

反応ノート

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