Phosgene → HCID 131721775, compound

Participants

Reaction Steps

A mixture of 90 mg (0.15 mmol) of tert-butyl 3SR,4RS,5RS)-4-[4-(3-benzyloxy-propoxy)-phenyl]-3-hydroxymethyl-5-(naphthalen-2-ylmethoxy)-piperidine-1-carboxylate [Example 148 (h)] and 60 mg (0.75 mmol) of lithium carbonate in 10 ml of dry tetrahydrofuran was cooled to 0° C. A solution of 0.90 ml (1.6 mmol) of phosgene in toluene (1.93N) was added dropwise thereto while cooling with ice. The mixture was stirred at room temperature overnight in order complete the reaction. The reaction mixture was evaporated under reduced pressure in order to remove the excess phosgene and the crude chloroformate obtained was taken up in 10 ml of tetrahydrofuran. This mixture was treated with 58 mg (0.38 mmol) of 1-(3-aminopropyl)-4-methylpiperizine and stirred at room temperature for 3 hours. For the working-up, the reaction mixture was diluted with 40 ml of methylene chloride and then extracted with 20 ml of water. The organic phase was dried over sodium sulphate and subsequently evaporated under reduced pressure. For purification, the residue was chromatographed on silica gel using a 95:5:0.1 mixture of methylene chloride, methanol and ammonia as the eluent. There were obtained 85 mg (73% of theory) of tert-butyl (3SR,4RS,5RS)-4-[4-(3-benzyloxy-propoxy)-phenyl]-3-[3-(4-methyl-piperazin-1-yl)-propylcarbamoyloxymethyl]-5-(naphthalen-2-ylmethoxy)-piperidine-1-carboxylate as a colourless solid; MS: 795 (M+H)+.

Provenance & Evidence