反应详情

温度

75 °C

The crude reaction mixture prepared in Step 5.1 was diluted with absolute ethanol (5 mL). 2-Aminoethanethiol (2.31 g, 30 mmol fresh dry material) was added and the mixture heated to 75° C. The reaction was monitored by TLC (silica gel, hexane-ethyl acetate (1:1 v/v) and methylene chloride-ethyl acetate-acetone (5:5:1 v/v)) and analytical HPLC. After 1.5 hours (>90% completion) the reaction was allowed to cool to room temperature to form a yellow crystalline solid. The solid material was collected by filtration and washed with ethanol-diethyl ether (1:1 v/v) and then hexane. Product was purified by column chromatography and then crystallization (methylene chloride-ethanol) to provide 3-[7-(2,4-dimethoxyphenyl)-2,3,6,7-tetrahydro-[1,4]thiazepin-5-yl]-4-hydroxy-6-methyl-pyran-2-one (6.81 g, 61%). LCMS: MH+375.6. Elemental Analysis: Calc: C 60.78, H 5.64, N 3.73 Found: 60.73, H 5.66, N 3.73. 1H NMR (CDCl3-TMS): d 14.3 (bs, 1H), 7.23 (m, 1H), 6.46 (m, 2H), 5.69 (s, 1H), 4.76 (d, 1H, J=13 Hz), 4.47 (d, 1H, J=11 Hz), 4.17 (m, 1H), 4.00 (m, 1H), 3.83 (s, 3H), 3.79 (s, 3H), 3.52 (t, 1H, J=11.5 Hz), 3.00 (t, 1H, J=11.5 Hz), 2.78 (dd, 1H, J=11.5,5 Hz), 2.09 (s, 3H). 1H NMR (DMSO-d6): d 13.7 (bs, 1H), 7.23 (dd, 1H, J=9, 3 Hz), 6.5 (m, 2H), 5.7 (s, 1H), 4.37 (d, 1H, J=13 Hz), 4.28 (d, 1H, J=10 Hz), 4.08 (m, 2H), 3.73 (s, 6H), 3.61 (t, 1H, J=11 Hz), 2.79 (m, 2H), 2.03 (s, 3H). 13C NMR JEOL, (DMSO-d6): d 183.84, 178.36, 163.42, 162.89, 160.32, 157.33, 128.28, 123.29, 107.76, 105.46, 99.16, 95.78, 56.26, 55.77, 46.0, 38.90, 34.19, 29.07, 19.68.

1. temperatureto cool to room temperature
2. customto form a yellow crystalline solid
3. filtrationThe solid material was collected by filtration
4. washwashed with ethanol-diethyl ether (1:1 v/v)
5. customProduct was purified by column chromatography
6. customcrystallization (methylene chloride-ethanol)