Formic Acid → Ethyl 1-methylpiperidine-4-carboxylate

HRID 37817

Reaction equation

HRID 37817 reaction equation
[NH:1]1[CH2:11][CH2:10][CH:4]([C:5]([O:7][CH2:8][CH3:9])=[O:6])[CH2:3][CH2:2]1.[CH:12](O)=O.C=O.C(=O)(O)[O-].[Na+]>ClCCl>[CH2:8]([O:7][C:5]([CH:4]1[CH2:3][CH2:2][N:1]([CH3:12])[CH2:11][CH2:10]1)=[O:6])[CH3:9]

Participants

6

Reactant 4

HCID 284Formic AcidHCID 712FormaldehydeHCID 70770Ethyl 4-piperidinecarboxylateHCID 516892Sodium Bicarbonate

Product 1

HCID 11062856Ethyl 1-methylpiperidine-4-carboxylateYield 61%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Ethyl isonipecotate (3.0 g, 19.1 mmol) was added to a mixture of 90% formic acid (10 mL) and 30% aqueous formaldehyde (10 mL, 100 mmol) then the mixture was heated at reflux for 24 h. After cooling, the mixture was concentrated in vacuo to give an oil which was dissolved in dichloromethane. Solid sodium bicarbonate (1 g) was added and the mixture stirred for 1 h then filtered. The filtrate was concentrated in vacuo to afford 1-methyl-piperidine-4-carboxylic acid ethyl ester (2.0 g, 61%) as a liquid, which was used as such for the next step.

Workup

  1. temperaturethe mixture was heated
  2. temperatureat reflux for 24 h
  3. temperatureAfter cooling
  4. concentrationthe mixture was concentrated in vacuo
  5. customto give an oil which
  6. filtrationthen filtered
  7. concentrationThe filtrate was concentrated in vacuo

Sources & evidence

ORD record
ord-f2ca1cc55a354d50b590eb5198221654
Source dataset
uspto-grants-2013_09
Patent number
US08524705B2

Linked notes

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