Formic Acid → 2-Methyl-2-(1-methyl-piperidin-3(r,s)-yl)-propionic acid methyl ester

HRID 507847Notes

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])([CH:7]1[CH2:12][CH2:11][CH2:10][N:9]([CH3:15])[CH2:8]1)[CH3:13]

Participants

Conditions

Temperature: 60 °C

Procedure

0.370 g of 2-methyl-2-piperidin-3(R,S)-yl-propionic acid methyl ester hydrochloride (Example 102) are dissolved in 0.5 ml of 3M NaOH. 2 ml of formic acid and 0.19 ml of formaldehyde (35% aqueous solution) are added and the reaction solution is warmed to 60° C. for 20 hours. The solution is cooled to room temperature, neutralised with 3M NaOH to pH 8-9 and extracted with dichloromethane (3×10 ml). The combined organic phases are washed with water (10 ml), dried over sodium sulphate and concentrated by evaporation. The residue is purified by means of flash chromatography (SiO2 60F) to provide the title compound as a colourless oil. Rf 0.19 (200:20:1 dichlormethane-methanol-25% conc. ammonia).

Workup

temperatureThe solution is cooled to room temperature
extractionextracted with dichloromethane (3×10 ml)
washThe combined organic phases are washed with water (10 ml)
dry with materialdried over sodium sulphate
concentrationconcentrated by evaporation
customThe residue is purified by means of flash chromatography (SiO2 60F)

Sources & evidence

ORD record: ord-cf09846df8ce4b3886e2a2bc19ddb654
Source dataset: uspto-grants-2010_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07786307B2

Reaction notes

Loading…