反应详情

7-(1-Hydroxyimino-ethyl)-1,2,4,5-tetrahydro-benzo[d]azepine-3-carboxylic acid tert-butyl ester (2.89 g, 9.5 mmol) was cooled to 0° C. in tetrahydrofuran (70 ml) under argon. Butyllithium (7.6 ml, 2.5M in hexane, 19 mmol) was added dropwise to give an orange solution which was stirred for 1 h. N-Methyl-N-methoxy acetamide (824 mg, 8 mmol) was added dropwise in tetrahydrofuran (30 ml) over 3 min. The mixture was stirred for 1 h and then poured into water (27 ml) and concentrated sulphuric acid (3 ml). The resulting mixture was heated to reflux for 1 h and then cooled and neutralised with solid sodium bicarbonate. The mixture was partitioned between dichloromethane (200 ml) and water (100 ml) and the layers separated. The aqueous portion was extracted with dichloromethane (2×100 ml) and the combined organic extracts were evaporated. The residue was treated with dichloromethane (50 ml) and di-tert-butyl dicarbonate (2.18 g, 10 mmol) and the mixture stirred for 20 min, washed with water (50 ml) and evaporated. The residue was treated with pyridine (10 ml) and hydroxylamine hydrochloride (0.77 g, 11 mmol) and the mixture stirred for 1 h. The solvent was evaporated and the residue dissolved in dichloromethane (50 ml) which was washed with dilute hydrochloric acid (3×50 ml, 0.5M). The solvent was evaporated and the residue was purified by silica gel chromatography (eluent dichloromethane) which gave the title compound as a colourless solid (447 mg, 61%).

1. customto give an orange solution which
2. stirringThe mixture was stirred for 1 h
3. temperatureThe resulting mixture was heated
4. temperatureto reflux for 1 h
5. customThe mixture was partitioned between dichloromethane (200 ml) and water (100 ml)
6. customthe layers separated
7. extractionThe aqueous portion was extracted with dichloromethane (2×100 ml)
8. customthe combined organic extracts were evaporated
9. stirringthe mixture stirred for 20 min
10. washwashed with water (50 ml)
11. customevaporated
12. stirringthe mixture stirred for 1 h
13. customThe solvent was evaporated
14. dissolutionthe residue dissolved in dichloromethane (50 ml) which
15. washwas washed with dilute hydrochloric acid (3×50 ml, 0.5M)
16. customThe solvent was evaporated
17. customthe residue was purified by silica gel chromatography (eluent dichloromethane) which