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

HRID 1838546

Reaction equation

HRID 1838546 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 colorless oil. MS-ESI: 172 [MH]30

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-789c9772a53844409028821bd48c8632
Source dataset
uspto-grants-2004_01
Patent number
US06673803B2

Linked notes

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