反应详情

Methylamine, generated by heating a mixture of methylamine hydrochloride (10 g) and sodium hydroxide pellets (18 g), was condensed (dry ice trap) into a solution of tetrahydro-4H-pyran-4-one (1.0 g, 10 mmol) in methanol (50 ml). 10% Pd on C (350 mg) was added and the mixture was hydrogenated at room temperature for 7 hours. The solids were filtered off and the filtrate concentrated under vacuum. The residue was dissolved in chloroform (70 ml) and triethylamine (2 ml) and a solution of [2,1,3]-benzoxadiazole-5-carbonylchloride (500 mg, 2.73 mmol) in chloroform (10 ml) was added slowly. After stirring the reaction mixture for minutes, the organic phase was extracted with 100 ml of water and sulfuric acid (→pH 2) and the aqueous phase re-extracted with chloroform (100 ml), dried over magnesium sulfate, and concentrated under vacuum to give an oil. The crude product was purified by silica gel chromatography eluting ethyl acetate/hexane (75:25) and chloroform/acetone (85:15) to give the title product as a white solid after crystallization from ethyl acetate. Mp=160-2° C., LC-MS, MH+=262; 1H NMR (300 MHz, CDCl3, 2 rotamers) δ 7.93 (d, 1H, J=9.0 Hz); 7.84 (s, 1H); 7.42 (d, 1H, J=9.0 Hz); 4.90-4.70 and 4.20-3.10 (m+m, 5H); 2.927 (s, 3H); 2.1-1.5 ppm (m, 4H).

1. temperatureby heating
2. filtrationThe solids were filtered off
3. concentrationthe filtrate concentrated under vacuum
4. dissolutionThe residue was dissolved in chloroform (70 ml)
5. extractionthe organic phase was extracted with 100 ml of water and sulfuric acid (→pH 2)
6. extractionthe aqueous phase re-extracted with chloroform (100 ml)
7. dry with materialdried over magnesium sulfate
8. concentrationconcentrated under vacuum
9. customto give an oil
10. customThe crude product was purified by silica gel chromatography
11. washeluting ethyl acetate/hexane (75:25) and chloroform/acetone (85:15)