反应详情

温度

-30 °C

The solution of 0.200 g of benzyl 4-(4-hydroxymethylphenyl)-3-[4-(3-methoxypropyl)-3,4-dihydro-2H-benzo[1,4]oxazin-6-ylmethoxy]piperidine-1-carboxylate (Example 270c) in 8 ml of carbon tetrachloride at 0° C. is admixed with 0.019 g of sodium hydride and then stirred for 20 minutes. The reaction mixture is admixed with 0.326 g of trichloroacetonitrile and stirred at 0° C. for 3 hours. Afterwards, a solution of 0.0322 g of 2-propanol in 5 ml of dichloromethane is added and the reaction mixture is cooled to −30° C. and admixed slowly with 0.108 g of trifluoromethanesulphonic acid. The reaction solution is stirred at −20° C. for 19 hours and subsequently poured onto 25 ml of aqueous saturated sodium hydrogencarbonate solution. The mixture is extracted twice with 50 ml of tert-butyl methyl ether. The combined organic phases are washed with 30 ml of brine, dried over sodium sulphate, filtered and concentrated by evaporation. The title compound is obtained as a yellowish oil from the residue by means of flash chromatography (SiO2 60F). Rf=0.15 (1:2 EtOAc-heptane); Rt=5.92.

1. customat 0° C.
2. stirringstirred at 0° C. for 3 hours
3. stirringThe reaction solution is stirred at −20° C. for 19 hours
4. extractionThe mixture is extracted twice with 50 ml of tert-butyl methyl ether
5. washThe combined organic phases are washed with 30 ml of brine
6. dry with materialdried over sodium sulphate
7. filtrationfiltered
8. concentrationconcentrated by evaporation