4-Methylmorpholine → Methanone, [4-(aminomethyl)-1-piperidinyl](2-chloro-3-pyridinyl)-

A solution of 2-chloropyridine-3-carboxylic acid (4.09 g) and 1-methylmorpholine (2.7 ml) in dichloromethane (100 ml) was stirred at -5° C. under nitrogen and ethyl chloroformate (2.4 ml) was added dropwise. After 10 minutes a solution of N-benzylidene-1-(4-piperidyl)methylamine (5.0 g) in dichloromethane (25 ml) was added and stirring continued at -5° C. for 2 hours then at ambient temperature for 18 hours. The solvent was removed in vacuo and the residue stirred with potassium hydrogen sulphate solution (1 M; 250 ml) for 5 hours. The mixture was filtered and the filtrate washed with dichloromethane (2×150 ml), basified with aqueous sodium hydroxide solution (5 M) and extracted with dichloromethane (3×150 ml). The combined extracts were dried over magnesium sulphate and the solvent was evaporated to give 4-(aminomethyl)-1-(2-chloro-3-pyridylcarbonyl)-piperidine (4.81 g) contaminated with some 1-methylmorpholine. This material was used in the next reaction without further purification.

1. waitat ambient temperature for 18 hours
2. customThe solvent was removed in vacuo
3. stirringthe residue stirred with potassium hydrogen sulphate solution (1 M; 250 ml) for 5 hours
4. filtrationThe mixture was filtered
5. washthe filtrate washed with dichloromethane (2×150 ml)
6. extractionextracted with dichloromethane (3×150 ml)
7. dry with materialThe combined extracts were dried over magnesium sulphate
8. customthe solvent was evaporated

ORD record

ord-6402878af0c04cbb83c341ff57d4649c

Source dataset

uspto-grants-1999_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05935973