反应详情

温度

0 °C

To a solution of 2-oxo-1,2,3,5-tetrahydro-benzo[e][1,4]diazepine-4-carboxylic acid tert-butyl ester (10.0 g, 38.16 mmol) in dry THF (300 mL) at 0° C., was added potassium tert-butoxide (6.4 g, 56.76 mmol) under nitrogen atmosphere and the reaction mixture was stirred at this temperature for 30 min followed by dropwise addition of diethylchlorophosphate (11 mL, 76.3.3 mmol). The reaction mixture was stirred at 0° C. for 40 min. This solution was transferred via cannula to a suspension of potassium tert-butoxide (12.86 g, 114.56 mmol) and ethyl isocyanoacetate (11.66 mL, 102.65 mmol) in dry THF (150 mL), kept in a separate flask at 0° C. under nitrogen atmosphere. When the addition was complete, the reaction mixture was allowed to come to r.t. and stirred for 45 min. during which the reaction was complete as confirmed by TLC. Reaction mixture was cooled to 0° C. and quenched with 10% acetic acid solution and stirred for 20 min. The crude compound was extracted with ethylacetate. The organic layer was washed with water, separated, dried over Na2SO4 and concentrated in vacuo to afford the crude compound which was purified by column chromatography (neutral alumina using neutral alumina, 3:7 EtOAc:Pet.Ether) to afford a viscous gel which was further purified by crystallisation from diethyl ether and hexane to afford 4H,6H-2,5,10b-triaza-benzo[e]azulene-3,5-dicarboxylic acid 5-tert-butyl ester 3-ethyl ester a white solid (4.4 g, 33%)

1. stirringThe reaction mixture was stirred at 0° C. for 40 min
2. customkept in a separate flask at 0° C. under nitrogen atmosphere
3. additionWhen the addition
4. customto come to r.t.
5. stirringstirred for 45 min. during which the reaction
6. customReaction mixture
7. customquenched with 10% acetic acid solution
8. stirringstirred for 20 min
9. extractionThe crude compound was extracted with ethylacetate
10. washThe organic layer was washed with water
11. customseparated
12. dry with materialdried over Na2SO4
13. concentrationconcentrated in vacuo
14. customto afford the crude compound which
15. customwas purified by column chromatography (neutral alumina using neutral alumina, 3:7 EtOAc:Pet.Ether)
16. customto afford a viscous gel which
17. customwas further purified by crystallisation from diethyl ether and hexane