反应详情

温度

20 °C

0.361 g of benzyl 4-[4(2-aminoethoxy]phenyl]-3-[4-(3-methoxypropyl)-3,4-dihydro-2H-benz[1,4]oxazin-6-ylmethoxy]piperidine-1-carboxylate (Example 184) is dissolved under argon in tetrahydrofuran. 2 g of 4 Å molecular sieve are added, followed by a solution of (4-fluorophenyl)acetaldehyde in 1 ml of tetrahydrofuran. The reaction mixture is stirred at 20° C. for 2 hours. 3 ml of methanol and 0.078 g of sodium acetate are added to the mixture. A solution of 0.055 g of sodium cyanoborohydride in 3 ml of methanol is added dropwise at 0° C. and the mixture is subsequently stirred at 0° C. over 1 hour. 10 ml of saturated aqueous sodium hydrogencarbonate solution are added and the mixture is subsequently filtered through Hyflo. The filtrate is extracted with ethyl acetate (2×20 ml)—the combined organic phases are washed with 20 ml of brine, dried over sodium sulphate and concentrated by evaporation. The title compound is obtained from the residue by means of flash chromatography (SiO2 60F). Rf=0.20 (200:5:1 dichloromethane-methanol-25% conc. ammonia); Rt=4.74.

1. addition2 g of 4 Å molecular sieve are added
2. stirringthe mixture is subsequently stirred at 0° C. over 1 hour
3. filtrationthe mixture is subsequently filtered through Hyflo
4. extractionThe filtrate is extracted with ethyl acetate (2×20 ml)—the combined organic phases
5. washare washed with 20 ml of brine
6. dry with materialdried over sodium sulphate
7. concentrationconcentrated by evaporation