反应详情

To a solution of 7-methylindazole-5-carboxaldehyde (8.80 g, 54.9 mmol) and N-methyl-dicyclohexylamine (23.6 mL, 110 mmol) in tetrahydrofuran (200 mL) at 0° C. was added chloromethyl methyl ether (7.50 mL, 1.8 equiv). The reaction was allowed to gradually warm to room temperature overnight. The reaction was concentrated, dissolved in diethyl ether, washed with water, then 1 M hydrochloric acid, then water, then brine, dried over magnesium sulfate, and concentrated to give an oil. The oil was dissolved in ethyl acetate and treated with hexanes until lasting turbidity. The suspension was heated until a clear solution was obtained and the flask placed in the freezer. The resulting crystalline solid was crushed with a spatula to break it up, reheated to dissolve some of the solids, and placed in the freezer. The solids were filtered, washed with very cold diethyl ether (−78° C.), and air-dried to give 5.43 g. The mother liquor was concentrated, redissolved in diethyl ether (ca. 20 mL), cooled to −78° C., and treated with a seed crystal of the product. After 1 h, the resulting solids were filtered, washed with cold diethyl ether (−78° C.), and air-dried to give an additional 1.05 g (total yield=58%). 1H-NMR (CDCl3, 500 MHz) δ 2.66 (s, 3H), 3.44 (s, 3H), 5.73 (s, 2H), 7.59 (s, 1H), 8.09 (s, 1H), 8.32 (s, 1H), 9.97 (s, 1H). Mass spec.: 205.19 (MH)+.

1. concentrationThe reaction was concentrated
2. dissolutiondissolved in diethyl ether
3. washwashed with water
4. dry with material1 M hydrochloric acid, then water, then brine, dried over magnesium sulfate
5. concentrationconcentrated
6. customto give an oil
7. temperatureThe suspension was heated until a clear solution
8. customwas obtained
9. customThe resulting crystalline solid was crushed with a spatula
10. dissolutionto dissolve some of the solids
11. filtrationThe solids were filtered
12. washwashed with very cold diethyl ether (−78° C.)
13. customair-dried
14. customto give 5.43 g
15. concentrationThe mother liquor was concentrated
16. dissolutionredissolved in diethyl ether (ca. 20 mL)
17. temperaturecooled to −78° C.
18. additiontreated with a seed crystal of the product
19. filtrationthe resulting solids were filtered
20. washwashed with cold diethyl ether (−78° C.)
21. customair-dried
22. customto give an additional 1.05 g (total yield=58%)