反应详情

温度

-5 °C

5-Chloropyridine-2-thiol (1.00 g, 6.87 mmol) synthesized in Example (119a) was dissolved in methylene chloride (30 mL)/1N hydrochloric acid (30 mL), and cooled to −5° C. To the reaction solution, ice-cooled 7% aqueous sodium perchlorate solution (30 mL) was added dropwise while being kept at 0° C. or below, and stirring was carried out as it is for 15 minutes. The organic layer was extracted with a reparatory funnel ice-cooled in advance, and cooled to −78° C., a methylene chloride solution (10 mL) of commercially available azetidine hydrochloride (2.24 mg, 17.7 mmol) and triethylamine (1.8 mL, 12.9 mmol) was added, and the temperature was raised to 0° C., followed by stirring for 30 minutes. To the reaction solution, water (50 mL) was added, and extraction was carried out twice with ethyl acetate (30 mL). The organic layer was washed with saturated brine, and subsequently dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the resulting residue was purified using silica gel column chromatography (elution solvent: ethyl acetate/hexane=5%-60%) to afford the desired compound (735 mg, yield 46%) as a white solid.

1. additionwas added dropwise
2. customwhile being kept at 0° C. or below
3. extractionThe organic layer was extracted with a reparatory funnel ice-
4. temperaturecooled in advance
5. temperaturecooled to −78° C.
6. temperaturethe temperature was raised to 0° C.
7. stirringby stirring for 30 minutes
8. extractionextraction
9. washThe organic layer was washed with saturated brine
10. dry with materialsubsequently dried over anhydrous magnesium sulfate
11. distillationThe solvent was distilled off under reduced pressure
12. customthe resulting residue was purified
13. washsilica gel column chromatography (elution solvent: ethyl acetate/hexane=5%-60%)