反应详情

温度

90 °C

To a mixture of 4-(5-bromo-2,3-dihydro-benzofuran-2-yl)-piperidine-1-carboxylic acid isopropyl ester (1.70 g), 4-(methoxycarbonyl)phenyl boronic acid (997 mg), in N,N-dimethylformamide (50 mL) a 2 M aqueous Na2CO3 solution (5.77 mL) is added. The mixture is sparged with argon for 10 min and PdCl2[1,1′-bis(diphenylphosphino)-ferrocene]*CH2Cl2 complex (377 mg) is added. The resulting mixture is stirred for 3 h at 90° C. After cooling to room temperature, water is added and the aqueous phase is extracted with ethyl acetate. The organic phase is concentrated and the residue is purified by HPLC on reversed phase (MeOH/H2O/TFA) yielding 4-[5-(4-methoxy-carbonyl-phenyl)-2,3-dihydro-benzofuran-2-yl]-piperidine-1-carboxylic acid isopropyl ester. The material was mixed with methanol (20 mL) and 1 M aqueous sodium hydroxide (11.5 mL). After heating for 5 h to 55° C. the mixture was cooled to 20° C. and acidified with 1 M aqueous HCl. The precipitate formed was filtered off, washed with water and dried in vacuo. LC (method 5): tR=1.59 min; Mass spectrum (ESI+): m/z=410 [M+H]+.

1. customThe mixture is sparged with argon for 10 min
2. additionPdCl2[1,1′-bis(diphenylphosphino)-ferrocene]*CH2Cl2 complex (377 mg) is added
3. temperatureAfter cooling to room temperature
4. additionwater is added
5. extractionthe aqueous phase is extracted with ethyl acetate
6. concentrationThe organic phase is concentrated
7. customthe residue is purified by HPLC on reversed phase (MeOH/H2O/TFA)