反应详情

A mixture of 2-amino-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-3-carboxylic acid ethyl ester (7 g, 0.02928 mol) and ethyl cyanoacetate (6.5 g, 0.05857 mol) in 72 ml of 1,4-dioxane was saturated with HCl gas while cooling the mixture. The mixture was stirred for 18 h at ambient temperature, then quenched with solid NaHCO3, diluted with 100 ml water and extracted with ethyl acetate (100 ml×3). The organic layer was separated, dried over Na2SO4 and concentrated under vacuum. The crude solid was triturated with diethyl ether (100 ml) to give (4-hydroxy-6,7,8,9-tetrahydro-5H-10-thia-1,3-diaza-benz[a]azulen-2-yl)-acetic acid ethyl ester (5.5 g, 62%) as a pale yellow solid. 1H NMR (400 MHz, CDCl3): δ 11.84 (brs, 1H), 4.18-4.28 (m, 2H), 3.78 (s, 2H), 3.22-3.32 (m, 2H), 2.80-2.90 (m, 2H), 1.83-1.93 (m, 2H), 1.58-1.75 (m, 5H), 1.26 (t, 3H); LC-MS: [M+H]=307.1 m/z.

1. temperaturewhile cooling the mixture
2. customquenched with solid NaHCO3
3. additiondiluted with 100 ml water
4. extractionextracted with ethyl acetate (100 ml×3)
5. customThe organic layer was separated
6. dry with materialdried over Na2SO4
7. concentrationconcentrated under vacuum
8. customThe crude solid was triturated with diethyl ether (100 ml)