反应详情

温度

20 °C

Dimethylsulphoxide (0.925 g) in dry dichloromethane (3 ml) was added dropwise to a stirred solution of oxalyl chloride (0.753 g) in dichloromethane (12 ml) at -60° under nitrogen, so as to maintain the internal temperature below -50°. The reaction mixture was stirred for 3 min before adding a solution of the product of Example 4 (2.0 g) in dichloromethane (5 ml) over 5 min. Stirring was continued for 15 min at -60° and triethylamine (2.72 g) was added with stirring. The reaction mixture was allowed to warm to 20° C., water (30 ml) was added, the layers were separated and the aqueous layer was further extracted with dichloromethane (30 ml). The combined organic extracts were dried and concentrated in vacuo to give a solid which was triturated under dry diethyl ether to give the free base of the title compound as an amorphous solid (1.54 g), m.p. 74°-76°. A portion (100 mg) of the free base was dissolved in a minimum amount of diethyl ether/ethyl acetate and treated with ethereal hydrogen chloride to precipitate the title compound as an amorphous solid (85 mg) m.p. 145°-147° (decomp.)

1. temperatureso as to maintain the internal temperature below -50°
2. stirringStirring
3. waitwas continued for 15 min at -60°
4. stirringwith stirring
5. customthe layers were separated
6. extractionthe aqueous layer was further extracted with dichloromethane (30 ml)
7. customThe combined organic extracts were dried
8. concentrationconcentrated in vacuo
9. customto give a solid which
10. customwas triturated under dry diethyl ether