tert-Butyl isocyanate → 3-tert-Butyl-6-chloro-1H-quinazoline-2,4-dione

Participants

Reaction Conditions

Reaction Steps

To a room temperature solution of 4-chloro-phenylamine (5.0 g, 39.19 mmol) was added di-tert-butyl dicarbonate (9.41 g, 43.11 mmol) portion-wise. The solution was heated to reflux, stirred for 2 hrs, cooled, concentrated, and dissolved in diethylether. The solution was washed with water, sodium bicarbonate and brine, dried over MgSO4, filtered, and concentrated to provide (4-chloro-phenyl)-carbamic acid tert-butyl ester (8.5 g) as a white solid, which was used with no further purification. To a −78° C. solution of (4-chloro-phenyl)-carbamic acid t-butyl ester (5.046, 23.30 mmol) in THF (232 mL) was added 32.9 mL of t-BuLi (1.7 M in pentane, 55.92 mmol) via cannula. The solution was stirred 10 min, warmed to −20° C. and stirred 2 hours further. To the −20° C. red solution was added t-butyl isocyanate (3.33 mL, 29.13 mmol). The solution was stirred at −20° C. for 1 hr, warmed to room temperature, stirred 2 hrs, then heated to reflux and stirred for 12 hrs. The reaction was cooled to room temperature, concentrated and dissolved in diethylether. The solution was washed with water, sodium bicarbonate and brine, dried over MgSO4, filtered, and concentrated to provide 5.87 g of white solid (100%). 1H NMR (300 MHz, CDCl3) δ ppm 1.76 (s, 9H), 6.91 (d, J=8.6 Hz, 1H), 7.48 (dd, J=2.2, 8.5 Hz, 1H), 7.97 (d, J=2.3 Hz, 1H), 9.22 (br s, 1H).

Provenance & Evidence