Imidazole → HCID 57244277, compound

Participants

Reaction Steps

To a solution of 1.5 g (2.2 mmol) of (3S,4R,5R)-3-hydroxymethyl-4-[4-[3-(2-methoxy-benzyloxy)-propoxy]-phenyl]-5-(4-methoxy-naphthalen-2-ylmethoxy)-piperidine-1-carboxylic acid tert-butyl ester [Example 13 (h)] in 40 ml of tetrahydrofurane were added 0.9 ml (6.7 mmol) of triethylamine and thereafter dropwise at 0° C. 512 mg (4.5 mmol) of methanesulphonyl chloride. The reaction solution was stirred at room temperature for 2 hours. For the working-up, the reaction solution was diluted with 50 ml of dichloromethane, extracted with 20 ml of saturated sodium hydrogencarbonate solution, dried over sodium sulfate and evaporated under reduced pressure. The solid crude mesylate was dissolved in 30 ml of N,N-dimethylformamide and thereafter added dropwise to a solution beforehand prepared of 456 mg (6.7 mmol) of imidazole and 322 mg (about 6.7 mmol) of sodium hydride dispersion in refined oil (55-65%) in 10 ml of N,N-dimethylformamide. The reaction mixture was stirred at 100° C. for 6 hours and thereafter evaporated under reduced pressure. The residue was taken up in 50 ml of dichloromethane and then extracted with 20 ml of saturated sodium hydrogencarbonate solution. The organic phase was separated and dried over sodium sulfate and subsequently evaporated under reduced pressure. For purification, the crude product was chromatographed on silica gel using a 98:2 mixture of dichloromethane and methanol as the eluent. There were obtained 1.4 g of (3R,4R,5R)-3-imidazol-1-ylmethyl-4-{4-[3-(2-methoxy-benzyloxy)-propoxy]-phenyl}-5-(4-methoxy-naphthalen-2-ylmethoxy)-piperidine-1-carboxylic acid tert-butyl ester as a yellowish foam; MS: 722 (M+H)+.

Provenance & Evidence