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

HRID 593379노트

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HRID 593379 반응식
[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

참가 물질

7

반응물 4

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

생성물 1

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

시약·촉매·용매 2

HCID 180Acetone용매HCID 6395Methanesulfonic Acid용매

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온도
145 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-4e51027f63e6476a9e998efc0ff7cc1a
출처 데이터셋
uspto-grants-2016_01
특허 번호
US09242959B2

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