Hydrochloric Acid → Methyl 5-{2-[((2R)-2-{[(benzyloxy)carbonyl]amino}-3-hydroxypropyl)oxy]phenyl}-6-cyclohexyl-3-methyl-4H-thieno[3,2-b]pyrrole-2-carboxylate

Participants

Reaction Conditions

Reaction Steps

Methyl 6-cyclohexyl-5-(2-hydroxyphenyl)-4-(methoxymethyl)-3-methyl-4H-thieno[3,2-b]pyrrole-2-carboxylate was dissolved in dioxane (0.036M) and the same volume of 6N HCl was added. The mixture was subjected to microwave irradiation (10 min @ 130° C.). All volatiles were evaporated and the product was enriched by prep. RP-HPLC. The product-containing fractions were lyophilised to give a green glassy solid. This material was dissolved in DMF (0.16M) and benzyl (4R)-2,2-dimethyl-4-({[(4-nitrophenyl)sulfonyl]oxy}methyl)-1,3-oxazolidine-3-carboxylate (excess, prepared according to Synthesis 1996, 189 in analogy to benzyl (4R)-2,2-dimethyl-4-({[(4-methylphenyl)sulfonyl]oxy}methyl)-1,3-oxazolidine-3-carboxylate from benzyl (4S)-4-(hydroxymethyl)-2,2-dimethyl-1,3-oxazolidine-3-carboxylate and substituting tosyl chloride with 4-nitrobenzenesulfonyl chloride) was added. The suspension was heated to 50° C. overnight. All volatiles were evaporated i. vac. and the residual material was purified by prep. RP-HPLC. The product fractions were evaporated and the residual material lyophilised from MeCN/water. A beige solid was obtained, which was dissolved dry MeOH (0.2M) and 1.25M HCl in MeOH (excess) was added. The solution was left stirring at RT. After 3 h all volatiles were evaporated and the residual material was subjected to purification by chromatography (PE:EtOAc, 6:4). After evaporation of the product fractions the product was obtained as a yellow powder (31%). MS (ES+) m/z 577 (M+H)+.

Provenance & Evidence