Hydrochloric Acid → 1-(6-Chloro-2-methoxy-pyrimidin-4-yl)-piperidine-4-carboxylic acid

HRID 216267Notes

Reaction equation

HRID 216267 reaction equation
[CH3:1][O:2][CH:3]1[N:8](Cl)[CH:7]=[CH:6][C:5]([Cl:10])=[N:4]1.Cl.[C:12](=[O:15])(O)[O-:13].[Na+].[CH3:17][CH2:18]O>>[Cl:10][C:5]1[N:4]=[C:3]([O:2][CH3:1])[N:8]=[C:7]([N:4]2[CH2:18][CH2:17][CH:7]([C:12]([OH:13])=[O:15])[CH2:6][CH2:5]2)[CH:6]=1

Participants

5

Reactant 4

HCID 313Hydrochloric AcidHCID 702EthanolHCID 516892Sodium BicarbonateHCID 866157142-Methoxy-3,6-dichloropyrimidine

Product 1

HCID 862401201-(6-Chloro-2-methoxy-pyrimidin-4-yl)-piperidine-4-carboxylic acidYield 70%

Conditions

Temperature
90 °C

Procedure

A mixture of 2-methoxy-3,6-dichloropyrimidine (635 mg, 3.55 mmol), isonipecotic hydrochloride (706 mg, 4.26 mmol) and sodium bicarbonate (895 mg, 10.65 mmol) in EtOH (12 mL) is heated at 90° C. for 15 hours. The mixture is concentrated, and the residue is taken up in water (30 mL) and extracted three times with EtOAc (25 mL). The aqueous solution is acidified to pH 3 with 10% citric acid and extracted three times with EtOAc (25 mL). The organic extracts from the acidic layer are combined and dried over magnesium sulfate, filtered and concentrated to afford 1-(6-chloro-2-methoxy-pyrimidin-4-yl)-piperidine-4-carboxylic acid [680 mg, 70%] as a solid.

Workup

  1. concentrationThe mixture is concentrated
  2. extractionextracted three times with EtOAc (25 mL)
  3. extractionextracted three times with EtOAc (25 mL)
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-5dfaa9a6349348c8824b723b0deed199
Source dataset
uspto-grants-2012_06
Patent number
US08193183B2

Reaction notes

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