反应详情

To a solution of 2-(2-(4-methoxy-2,6-dimethylphenylsulfonyl)benzyloxy)acetic acid [carboxylic acid 1] (0.5 mmol) in dichloromethane (5 ml) were added DIPEA (4 eq.), EDCI. HCl (1.2 eq) and HOBt (1 eq.). Then a mixture of Boc-deprotected tert-butyl 4-(pyridin-3-yl)-4-(2-(pyrrolidin-1-yl)ethyl)piperidine-1-carboxylate (0.62 mmol) [deprotected using standard reaction conditions: dichloromethane (3 ml), TFA (3 eq.) and concentration in vacuo] and DIPEA (2 eq.) in dichloromethane (3 ml) was added dropwise at ice-cold reaction conditions. The reaction mixture was stirred at room temperature overnight. The mixture was diluted with dichloromethane, washed with saturated ammonium chloride, brine, saturated sodium bicarbonate solution and again brine. The organic layer was dried over anhydrous sodium sulfate and concentrated in vacuo. The crude product was purified by column chromatography (silica, methanol/dichloromethane). The free base of the desired compound was dissolved in dioxane (3 ml), stirred in dioxane saturated with HCl for 1 h and then concentrated under reduced pressure to give the desired product.

1. additionwas added dropwise at ice-cold reaction conditions
2. washwashed with saturated ammonium chloride, brine, saturated sodium bicarbonate solution and again brine
3. dry with materialThe organic layer was dried over anhydrous sodium sulfate
4. concentrationconcentrated in vacuo
5. customThe crude product was purified by column chromatography (silica, methanol/dichloromethane)
6. dissolutionThe free base of the desired compound was dissolved in dioxane (3 ml)
7. stirringstirred in dioxane saturated with HCl for 1 h
8. concentrationconcentrated under reduced pressure