4-Piperidinol, 1-methyl- → Oxalate

HRID 593384Notes

Reaction equation

HRID 593384 reaction equation
[OH:1][CH:2]([C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][N:11]=1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[OH:9].[OH:16][CH:17]1[CH2:22][CH2:21][N:20]([CH3:23])[CH2:19][CH2:18]1.O.C1(C)C=CC(S(O)(=O)=[O:32])=CC=1.[C:36]([O-:39])([OH:38])=O.[Na+]>C1(C)C=CC=CC=1.CN1CCCC1=O.CC(C)=O>[CH3:23][N:20]1[CH2:21][CH2:22][CH:17]([O:1][CH:2]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][N:11]=2)[C:3]2[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=2[OH:9])[CH2:18][CH2:19]1.[C:17]([O-:16])(=[O:32])[C:36]([O-:39])=[O:38]

Participants

9

Reactant 4

HCID 660484-Piperidinol, 1-methyl-HCID 516892Sodium BicarbonateHCID 521998p-Toluenesulfonic acid monohydrateHCID 14937588HCID 14937588, compound

Product 2

HCID 71081OxalateHCID 72694420HCID 72694420, compound

Reagents, catalysts & solvents 3

HCID 180AcetoneSolventHCID 1140TolueneSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

A mixture of 2-(hydroxypyridin-2-ylmethyl)phenol (0.27 g), 4-hydroxy-1-methylpiperidine (0.31 g) and para-toluenesulfonic acid, monohydrate (0.89 g) in toluene (20 mL) and 1-methyl-2-pyrrolidinone (1 mL) is heated for 3 hours in a Dean-Stark apparatus. The mixture is cooled back to room temperature, treated with aqueous NaHCO3 and extracted twice with ethyl acetate. Pooled organic extracts are washed with brine, dried over magnesium sulfate and concentrated. The residue is purified by column chromatography over silica gel (gradient dichloromethane/methanol/ammonia from 100/0/0.5 to 95/5/0.5) to afford the pure base that is then converted into its oxalate salt in acetone to give 2-[(1-methylpiperidin-4-yloxy)pyridin-2-ylmethyl]phenol, oxalate as a solid melting at 70° C.

Workup

  1. temperatureis heated for 3 hours in a Dean-Stark apparatus
  2. extractionextracted twice with ethyl acetate
  3. washPooled organic extracts are washed with brine
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated
  6. customThe residue is purified by column chromatography over silica gel (gradient dichloromethane/methanol/ammonia from 100/0/0.5 to 95/5/0.5)
  7. customto afford the pure base that

Sources & evidence

ORD record
ord-98ee7f7f92d0435281df2b3c93d34e48
Source dataset
uspto-grants-2016_01
Patent number
US09242959B2

Reaction notes

Loading…