Methanesulfonic Acid → Oxalate

HRID 593386Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 593386
[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]

Komponenten

8

Edukt 4

HCID 6395Methanesulfonic AcidHCID 660484-Piperidinol, 1-methyl-HCID 516892Sodium BicarbonateHCID 86703874HCID 86703874, Verbindung

Produkt 2

HCID 71081OxalateHCID 72694516HCID 72694516, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 111,2-DichloroethaneLösungsmittelHCID 180AcetoneLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

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.

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-44971b49ee2a4ee3b681401dcac22c20
Quelldatensatz
uspto-grants-2016_01
Patentnummer
US09242959B2

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