2-Methylpiperidine → HCID 58924819, compound

Participants

Reaction Steps

A solution of a mixture of 2-iodo-thiazole-4-carboxylic acid ethyl ester and 2-bromo-thiazole-4-carboxylic acid (from Step 2; 11.5 g), N,N-dimethylaminopyridine (11.2 g, 91.7 mmol), HOBT (10.0 g, 74.0 mmol), 1-(3-dimethylaminopropyl)-3-ethyl-carbodiimide hydrochloride (14.0 g, 73.0 mmol), and 2-methyl-piperidine (8 mL, 68.1 mol) in dry dichloromethane (150 mL) and dry acetonitrile (20 mL) was stirred at room temperature for 72 h. At this time, the reaction mixture was concentrated in vacuo. The resulting solution was diluted with dichloromethane (25 mL) and 1 N HCl (250 mL). The mixture was stirred for several hours at room temperature. At this time, the mixture was filtered and the solids were washed with dichloromethane (200 mL). The aqueous layer was extracted with dichloromethane (2×250 mL). The combined organic layers were washed with water (450 mL) and brine (450 mL). The organic layer was dried over MgSO4, filtered, concentrated in vacuo, and purified by flash column chromatography eluting with a gradient of ethyl acetate in hexanes to give (2-iodo-thiazol-4-yl)-(2-methyl-piperidin-1-yl)-methanone (8.1 g, 30% yield from 2-amino-thiazole-4-carboxylic acid ethyl ester hydrobromide).

Provenance & Evidence