反应详情

6.0 g (32 mmole) of 3 is placed in a 250 mL single neck round bottom flask and 30 mL of acetonitrile is added to create a pale yellow slurry. 6.0 ml (64 mmole, 2 equiv.) of phosphorus oxychloride is added changing the slurry to a darker color. The flask is fitted with a reflux condenser and a dry tube filled with anhydrous CaCl2 is fitted to the top of the condenser. The reaction mixture is heated at reflux and becomes a dark red liquid. After the reaction is completed (2.5 h), the mixture is cooled to ambient temperature and placed in an ice water bath. Ice water (150 mL) is slowly poured into the reaction mixture with stirring to decompose the phosphorus oxychloride into HCl and H3PO4, resulting in formation of a pink solid. The solid is collected by filtration and washed three times with 50 of Milli-Q water. The solid is transferred to a 250 rat, beaker, followed by addition of 100 rill, of water to form a suspension. Subsequently, 1N NaOH is added until the aqueous suspension is at pH=8, and the mixture is stirred for 5 minutes to remove all trace of starting material contaminants. The solid is filtered and washed 3 times with 100 mL of water to wash out the excess base. The solid is dried over a medium frit sintered glass funnel in vacuo to provide 4 as a light pink powder in 96% yield. [See Contreras, J M et al. Journal of Medicinal Chemistry, 2001, 44(17), 2707-2718; Nelson, D A. US 20050137397A1.]

1. customThe flask is fitted with a reflux condenser and a dry tube
2. customis fitted to the top of the condenser
3. temperatureThe reaction mixture is heated
4. temperatureat reflux
5. custom(2.5 h)
6. customplaced in an ice water bath
7. customresulting in formation of a pink solid
8. filtrationThe solid is collected by filtration
9. washwashed three times with 50 of Milli-Q water
10. additionfollowed by addition of 100 rill, of water
11. customto form a suspension
12. stirringthe mixture is stirred for 5 minutes
13. customto remove all trace of starting material contaminants
14. filtrationThe solid is filtered
15. washwashed 3 times with 100 mL of water
16. washto wash out the excess base
17. customThe solid is dried over a medium frit sintered glass funnel in vacuo