Formic Acid → ethyl (3R)-1-methylpiperidine-3-carboxylate

HRID 454001

Reaction equation

HRID 454001 reaction equation
[NH:1]1[CH2:11][CH2:10][CH2:9][C@@H:3]([C:4]([O:6][CH2:7][CH3:8])=[O:5])[CH2:2]1.[CH:12](O)=O.C(=O)([O-])O.[Na+].[OH-].[Na+]>C=O>[CH3:12][N:1]1[CH2:11][CH2:10][CH2:9][C@@H:3]([C:4]([O:6][CH2:7][CH3:8])=[O:5])[CH2:2]1

Participants

6

Reactant 4

HCID 284Formic AcidHCID 14798Sodium HydroxideHCID 185582ethyl (3R)-piperidine-3-carboxylateHCID 516892Sodium Bicarbonate

Product 1

HCID 736036ethyl (3R)-1-methylpiperidine-3-carboxylateYield 73%

Reagents, catalysts & solvents 1

HCID 712FormaldehydeSolvent

Procedure

(R)-Ethyl nipecotate (5.7 g 365 mmol), (prepared by resolution of ethyl nipecotate by treatment with L(+)-tartaric acid as described in J. Org. Chem. 1991, (56), 1168), was dissolved in 38.5% aqueous formaldehyde solution (45 ml) and formic acid (90 ml) and the mixture heated at reflux for 18 hours. The mixture was allowed to cool and added dropwise to cooled saturated aqueous sodium hydrogen carbonate solution. The mixture was adjusted to pH12 by addition of sodium hydroxide and the mixture was extracted with methylene chloride. The organic extract was washed with brine, dried (MgSO4) and the solvent removed by evaporation to give (R)-ethyl 1-methylpiperidine-3-carboxylate (4.51 g, 73%) as a colourless oil.

Workup

  1. temperatureat reflux for 18 hours
  2. temperatureto cool
  3. additionadded dropwise
  4. extractionthe mixture was extracted with methylene chloride
  5. extractionThe organic extract
  6. washwas washed with brine
  7. dry with materialdried (MgSO4)
  8. customthe solvent removed by evaporation

Sources & evidence

ORD record
ord-9aadfca64f224018952b4241356f9dbd
Source dataset
uspto-grants-2013_07
Patent number
US08492560B2

Linked notes

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