反应详情

温度

35 °C

Triethylamine (0.759 g, 7.50 mmol) was added to a suspension of 5-bromo-8-hydroxy-1,6-naphthyridine-7-carboxylic acid methyl ester (6, 1.415 g, 5.000 mmol) in chloroform (5 mL) over 5 min maintaining the temperature at 20-50° C. to give a yellow suspension. p-Toluenesulfonyl chloride (1.15 g, 6.00 mmol) was added over 5 min maintaining the temperature at 20-40° C. to give a yellow solution. The mixture was aged at 40° C. for 2 h during which a crystalline solid precipitated out of the mixture and the color faded (HPLC analysis indicated <0.5% starting material remaining). The mixture was cooled to 20° C. over 15 min. MeOH (10 mL) was added over 30 min then a 1:1 mixture of MeOH:water (10 mL) was added over 30 min. The mixture was cooled to −40° C. over 30 min and aged at −40° C. for 30 min. The cold mixture was filtered and the solid was washed with 1:1 MeOH:water (10 mL), MeOH (5 mL), MTBE (10 mL) and hexanes (10 mL) all at 10-20° C. The off-white crystalline solid was dried under a stream of nitrogen to provide 2.112 g (97% yield) of 5-bromo-8-(p-toluenesulfonyloxy)-1,6-naphthyridine-7-carboxylic acid methyl ester (7).

1. customto give a yellow suspension
2. temperaturemaintaining the temperature at 20-40° C.
3. customto give a yellow solution
4. customa crystalline solid precipitated out of the mixture
5. temperatureThe mixture was cooled to 20° C. over 15 min
6. additionMeOH (10 mL) was added over 30 min
7. additiona 1:1 mixture of MeOH
8. additionwater (10 mL) was added over 30 min
9. temperatureThe mixture was cooled to −40° C. over 30 min
10. waitaged at −40° C. for 30 min
11. filtrationThe cold mixture was filtered
12. washthe solid was washed with 1:1 MeOH
13. customat 10-20° C
14. customThe off-white crystalline solid was dried under a stream of nitrogen