反应详情

温度

-78 °C

DMSO (5.19 mL) was added dropwise over a period of 5 minutes to a solution of 8-hydroxy-2-[6-(2,2,2-trifluoro-ethoxy)-pyridin-3-yl]-2-aza-spiro[4.5]decan-1-one (9.53 g, obtained in example 108, step 3) in dichloromethane (100 mL) that was cooled down to −78° C. in a CO2/acetone-bath. After 5 minutes, oxalylchloride (3.04 mL) was added dropwise over a period of 10 minutes and stirring was continued for 30 minutes at −78° C. Then, triethylamine (17 mL) was added dropwise over a period of 10 minutes to the reaction mixture and after 5 minutes, the mixture was allowed to warm to 20° C. The reaction mixture was poured into ice/water and was acidified with 2M aqueous HCl solution (150 mL) to pH 3. The aqueous phase was extracted two times with dichloromethane and the combined organic layers were washed with brine, dried over Na2SO4 and filtered. The solvent was evaporated and the residue was purified by flash chromatography (silica gel, gradient of dichloromethane in acetonitrile) to give the title compound as a light yellow solid (6.19 g, 80%). MS (m/e): 343.2 [MH+].

1. waitwas continued for 30 minutes at −78° C
2. temperatureto warm to 20° C
3. extractionThe aqueous phase was extracted two times with dichloromethane
4. washthe combined organic layers were washed with brine
5. dry with materialdried over Na2SO4
6. filtrationfiltered
7. customThe solvent was evaporated
8. customthe residue was purified by flash chromatography (silica gel, gradient of dichloromethane in acetonitrile)