反应详情

0.301 g of trans-4-(4-methoxycarbonylcyclohexyloxy)benzoic acid (1.08 mmol, 1 eq.) is placed in 5 mL of dichloromethane at room temperature. 0.36 mL of diisopropylethylamine (2.16 mmol, 2 eq.), 0.604 g of bromotris-pyrrolidinophosphonium hexafluorophosphonate (1.30 mmol, 1.2 eq.) and 0.207 g of 5-benzyl-1,3,4-thiadiazol-2-amine (1.08 mmol, 1 eq.) are successively added. 2 mL of DMF are then added. The reaction mixture is stirred for 18 hours at room temperature. 0.1 mL of diisopropylethylamine (0.6 mmol, 0.55 eq.), 0.2 g of bromotris-pyrrolidinophosphonium hexafluorophosphonate (0.43 mmol, 0.4 eq.) and 0.05 g of 5-benzyl-1,3,4-thiadiazol-2-amine (0.26 mmol, 0.24 eq.) are added. The reaction medium is stirred at 50° C. for 6 hours, diluted in dichloromethane, and washed with water and with saturated aqueous sodium bicarbonate solution. The organic phase is dried over magnesium sulfate and concentrated, and the residue is chromatographed on silica gel, eluting with a gradient of ethyl acetate in heptane ranging from 10% to 70%. The fractions of interest are evaporated. The solid obtained is triturated in ethanol to give 0.128 g of methyl trans-4-[4-(5-benzyl[1.3.4]thiadiazol-2-ylcarbamoyl)phenoxy]cyclohexanecarboxylate.

1. stirringThe reaction medium is stirred at 50° C. for 6 hours
2. washwashed with water and with saturated aqueous sodium bicarbonate solution
3. dry with materialThe organic phase is dried over magnesium sulfate
4. concentrationconcentrated
5. customthe residue is chromatographed on silica gel
6. washeluting with a gradient of ethyl acetate in heptane ranging from 10% to 70%
7. customThe fractions of interest are evaporated
8. customThe solid obtained
9. customis triturated in ethanol