Methanesulfonic Acid → Oxalate

HRID 593386Notes

Reaction equation

HRID 593386 reaction equation
[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]

Participants

8

Reactant 4

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

Product 2

HCID 71081OxalateHCID 72694516HCID 72694516, compound

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 180AcetoneSolvent

Conditions

Temperature
80 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-44971b49ee2a4ee3b681401dcac22c20
Source dataset
uspto-grants-2016_01
Patent number
US09242959B2

Reaction notes

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