反应详情

温度

120 °C

In a 100 ml round-bottomed flask, 0.600 g (2.08 mmol) of 31 were dissolved in 15.5 ml (417.6 mmol, ρ=1.22 g/ml) of formic acid while cooling in ice and 5.1 ml of formaldehyde solution (183.6 mmol, ρ=1.22 g/ml, <37% in water) were added. The ice bath was subsequently removed and the mixture was heated at an oil bath temperature of 120° C. for 48 hours. After cooling to 0° C., 50% strength NaOH was added while cooling in ice until the pH of the mother liquor had risen to 12. The mixture was subsequently extracted three times with 50 ml of DCM and the combined organic phases were dried over Na2SO4. After distilling off the solvent on a rotary evaporator, the crude product was purified by flash chromatography on silica gel (CHCl3/isohexane/NEt3, 10:2:1). This gave 0.564 g (1.87 mmol, 90%) of a yellow solid. Rf=0.40 (CHCl3/isohexane/NEt3, 10:2:1). 1H NMR: (400 MHz, CDCl3): δ=2.85 (s, 3H, CH3), 4.42 (s, 1H, N—H), 4.44 (d, 3J=3.6 Hz, 1H, H-3), 4.95 (d, 3J=3.6 Hz, 1H, H-2), 6.50 (d, 3J=5.2 Hz, 1H, H-8), 6.64 (dd, 4J=2.8 Hz, 3J=9.2 Hz, 2H, 2,6-phenyl-H), 6.90 (m, 2H, 2,6-phenyl-H) 7.05 (m, 2H, phenyl-H), 7.16 (m, 4H, phenyl-H), 7.82 (s, 1H, H-5), 7.84 (d, 3J=5.2 Hz ppm. 13C NMR (75 MHz, CDCl3): δ=37.2 (CH3), 57.8 (C-3), 67.9 (C-2), 107.6 (C-8), 127.4-128.5 (phenyl-C), 131.3 (C-5), 131.6 (Cq, C-4a) 137.4, 138.8 (Cq, phenyl-C), 139.9 (C-7, C-8a) ppm. MS (EI): m/e (%) 302 (22), 301 (M+, 100), 300 (5), 286 (5), 224 (10), 222 (4), 211 (13), 210 (87), 209 (3), 208 (6), 195 (11), 181 (6), 179 (3), 178 (3), 178 (3), 150 (7), 132 (3), 127 (3), 120 (3), 104 (4); 92 (3), 91 (31), 85 (4), 83 (6), 78 (4), 77 (5); IR (neat): ν=3200 (w), 3158 (w), 3029 (w), 2948 (w), 2881 (w), 2824 (w), 1578 (s), 1516 (vs), 1491 (m), 1452 (m), 1421 (m), 1374 (w), 1353 (w), 1326 (w), 1294 (w), 1256 (m), 1235 (m), 1199 (w), 1157 (m), 1131 (m), 1103 (w), 1073 (m), 1054 (m), 1031 (m), 1013 (m), 969 (w), 922 (w), 842 (w), 810 (s), 766 (s), 755 (m), 733 (m), 641 (vs) cm−1. HRMS (EI): calculated for C20H19N3 301.1574 [M+], found: 301.1559.

1. temperaturewhile cooling in ice
2. customThe ice bath was subsequently removed
3. temperatureAfter cooling to 0° C.
4. addition50% strength NaOH was added
5. temperaturewhile cooling in ice until the pH of the mother liquor
6. extractionThe mixture was subsequently extracted three times with 50 ml of DCM
7. dry with materialthe combined organic phases were dried over Na2SO4
8. distillationAfter distilling off the solvent
9. customon a rotary evaporator
10. customthe crude product was purified by flash chromatography on silica gel (CHCl3/isohexane/NEt3, 10:2:1)