Methanesulfonic Acid → Oxalate

HRID 593386ノート

反応式

HRID 593386 の反応式
[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH:9]([C:11]2[CH:16]=[CH:15][C:14]([F:17])=[CH:13][N:12]=2)[OH:10])=[C:6]([OH:8])[CH:7]=1.[OH:18][CH:19]1[CH2:24][CH2:23][N:22]([CH3:25])[CH2:21][CH2:20]1.CS(O)(=O)=[O:28].[C:31](=[O:34])([O-:33])O.[Na+]>ClCCCl.CC(C)=O>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH:9]([C:11]2[CH:16]=[CH:15][C:14]([F:17])=[CH:13][N:12]=2)[O:10][CH:19]2[CH2:24][CH2:23][N:22]([CH3:25])[CH2:21][CH2:20]2)=[C:6]([OH:8])[CH:7]=1.[C:19]([O-:18])(=[O:28])[C:31]([O-:33])=[O:34]

参加物

8

反応物 4

HCID 6395Methanesulfonic AcidHCID 660484-Piperidinol, 1-methyl-HCID 516892Sodium BicarbonateHCID 86703874HCID 86703874、化合物

生成物 2

HCID 71081OxalateHCID 72694516HCID 72694516、化合物

試薬・触媒・溶媒 2

HCID 111,2-Dichloroethane溶媒HCID 180Acetone溶媒

反応条件

温度
80 °C

実験手順

A mixture of 5-fluoro-2-[(5-fluoropyridin-2-yl)hydroxymethyl]phenol (100 mg), 4-hydroxy-1-methylpiperidine (97 mg), methanesulfonic acid (109 μL) in 1,2-dichloroethane (3 mL) is heated for 1 hour at 80° C. The mixture is cooled back to room temperature, slowly basified with a saturated aqueous sodium hydrogencarbonate solution and extracted with dichloromethane. 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 oxalate salt in acetone to give 5-fluoro-2-[(5-fluoropyridin-2-yl)(1-methylpiperidin-4-yloxy)methyl]phenol, oxalate melting at 105° C. HPLC-MS method A, RT=3.66 min.

後処理

  1. temperatureThe mixture is cooled back to room temperature
  2. extractionextracted with dichloromethane
  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-44971b49ee2a4ee3b681401dcac22c20
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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