Formic Acid → (R)-2-methyl-2-(1-methyl-piperidin-3-yl)-propionic acid methyl ester

HRID 252388Notes

Reaction equation

HRID 252388 reaction equation
Cl.[CH3:2][O:3][C:4](=[O:14])[C:5]([CH3:13])([CH:7]1[CH2:12][CH2:11][CH2:10][NH:9][CH2:8]1)[CH3:6].[CH:15](O)=O.C=O>[OH-].[Na+]>[CH3:2][O:3][C:4](=[O:14])[C:5]([CH3:6])([C@H:7]1[CH2:12][CH2:11][CH2:10][N:9]([CH3:15])[CH2:8]1)[CH3:13]

Participants

5

Reactant 3

HCID 284Formic AcidHCID 712FormaldehydeHCID 66887928Methyl 2-methyl-2-(piperidin-3-yl)propanoate hydrochloride

Product 1

HCID 66889160(R)-2-methyl-2-(1-methyl-piperidin-3-yl)-propionic acid methyl ester

Reagents, catalysts & solvents 1

HCID 14798Sodium HydroxideSolvent

Procedure

0.992 g of 2-methyl-2-piperidin-3-yl-propionic acid methyl ester hydrochloride are dissolved in 2.2 ml of 2M NaOH. The solution is stirred for 10 minutes at room temperature. 7 ml of formic acid and 0.900 ml of 36% aqueous formaldehyde solution are added and the mixture is warmed to 60° C. for 16 hours. The solution is concentrated under reduced pressure. The residue is taken up water and the pH adjusted to 8-9 with saturated sodium carbonate solution. The mixture is extracted with ethyl acetate (3×) and tetrahydrofuran (2×)—the combined extracts are dried over sodium sulphate and concentrated. The title compound is obtained as a yellow oil from the residue by means of flash chromatography (SiO2 60F). Rf=0.23 (200:20:1 dichloromethane/methanol/25% conc. ammonia).

Workup

  1. temperaturethe mixture is warmed to 60° C. for 16 hours
  2. concentrationThe solution is concentrated under reduced pressure
  3. extractionThe mixture is extracted with ethyl acetate (3×) and tetrahydrofuran (2×)—the combined extracts
  4. dry with materialare dried over sodium sulphate
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-e8d1d230943744adb9e6cbf893f824e3
Source dataset
uspto-grants-2011_01
Patent number
US07868036B2

Reaction notes

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