Water → 2-[(2-Fluoro-5-trifluoromethoxyphenyl)(1-methylpiperidin-4-yloxy)methyl]pyridine

HRID 593379ノート

反応式

HRID 593379 の反応式
[F:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:9]([F:12])([F:11])[F:10])=[CH:4][C:3]=1[CH:13]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][N:16]=1)[OH:14].O[CH:22]1[CH2:27][CH2:26][N:25]([CH3:28])[CH2:24][CH2:23]1.O.[OH-].[Na+]>CS(O)(=O)=O.CC(C)=O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:9]([F:12])([F:11])[F:10])=[CH:4][C:3]=1[CH:13]([O:14][CH:22]1[CH2:27][CH2:26][N:25]([CH3:28])[CH2:24][CH2:23]1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][N:16]=1

参加物

7

反応物 4

HCID 962WaterHCID 14798Sodium HydroxideHCID 660484-Piperidinol, 1-methyl-HCID 86703870(2-Fluoro-5-trifluoromethoxyphenyl)pyridin-2-ylmethanol

生成物 1

HCID 721962382-[(2-Fluoro-5-trifluoromethoxyphenyl)(1-methylpiperidin-4-yloxy)methyl]pyridine

試薬・触媒・溶媒 2

HCID 180Acetone溶媒HCID 6395Methanesulfonic Acid溶媒

反応条件

温度
145 °C

実験手順

A mixture of (2-fluoro-5-trifluoromethoxyphenyl)pyridin-2-ylmethanol (340 mg) and 4-hydroxy-1-methylpiperidine (273 mg) in methanesulfonic acid (1.5 mL) is heated in a sealed tube at 145° C. for 24 hours and then at 155° C. for 7 hours. The mixture is cooled back to room temperature, poured into water which is then made alkaline with concentrated sodium hydroxide solution. The aqueous phase is extracted with diethyl ether. Pooled extracts are dried over magnesium sulphate and concentrated under reduced pressure. The residue is purified by column chromatography over silica gel (gradient dichloromethane/methanol/ammonia from 95/5/0.5 to 90/10/0.5) to afford the pure base that is then converted into its dioxalate salt in acetone to give 2-[(2-fluoro-5-trifluoromethoxyphenyl)(1-methylpiperidin-4-yloxy)methyl]pyridine, dioxalate melting at 45° C.

後処理

  1. temperatureThe mixture is cooled back to room temperature
  2. extractionThe aqueous phase is extracted with diethyl ether
  3. dry with materialPooled extracts are dried over magnesium sulphate
  4. concentrationconcentrated under reduced pressure
  5. customThe residue is purified by column chromatography over silica gel (gradient dichloromethane/methanol/ammonia from 95/5/0.5 to 90/10/0.5)
  6. customto afford the pure base that

出典と根拠

ORDレコード
ord-4e51027f63e6476a9e998efc0ff7cc1a
出典データセット
uspto-grants-2016_01
特許番号
US09242959B2

反応ノート

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