反应详情

温度

45 °C

To a solution of ethyl 3-oxobutanoate (1.3 g, 10 mmol) and 2-methylpropan-2-amine (0.73 g, 10 mmol) in toluene (15 mL) were added anhydrous magnesium sulfate (3.0 g, 25 mmol) and Montmorillonite K10 (3.0 g, 10 mmol). The resulting mixture was stirred at 45° C. for 14 h and then cooled to room temperature. The mixture was diluted with anhydrous ethyl ether, filtered and washed with ethyl ether. The filtrate and washings were combined and concentrated under reduced pressure. The residue was dissolved in THF (60 mL), 5-chloro-2-methoxybenzoyl isothiocyanate (2.16 g, 9.5 mmol) was added and the mixture was stirred at ambient temperature for 2 h. Iodine (2.4 g, 9.5 mmol) was added followed by addition of MeOH (100 mL) and pyridine (10 mL). The mixture was left overnight at room temperature and then treated with ethyl acetate and a saturated solution of sodium bicarbonate for additional 1 h. The layers were separated and the aqueous layer was extracted with ethyl acetate. The extracts were combined, washed with brine, dried with MgSO4 and concentrated under reduced pressure. The solid was triturated with hexane-ethyl ether (1:1) to provide 2.8 g of the title compound. 1H NMR (300 MHz, DMSO-d6) δ ppm 1.37 (t, 3 H), 1.74 (s, 9 H), 2.76 (s, 3 H), 3.82 (s, 3 H), 4.32 (q, J=6.9 Hz, 2 H), 7.16 (d, J=8.7 Hz, 1 H), 7.52 (dd, J=8.7, 2.8 Hz, 1 H), 8.01 (d, J=3.2 Hz, 1 H); MS (DCI/NH3) m/z 411 (M+H)+.

1. temperaturecooled to room temperature
2. filtrationfiltered
3. washwashed with ethyl ether
4. concentrationconcentrated under reduced pressure
5. dissolutionThe residue was dissolved in THF (60 mL)
6. stirringthe mixture was stirred at ambient temperature for 2 h
7. waitThe mixture was left overnight at room temperature
8. customThe layers were separated
9. extractionthe aqueous layer was extracted with ethyl acetate
10. washwashed with brine
11. dry with materialdried with MgSO4
12. concentrationconcentrated under reduced pressure
13. customThe solid was triturated with hexane-ethyl ether (1:1)