反応 #61488

反応方程式

sodium bicarbonate

di-tert-butyl dicarbonate

hydroxylamine hydrochloride

Butyllithium

N-Methyl-N-methoxy acetamide

sulphuric acid

7-(1-Hydroxyimino-ethyl)-1,2,4,5-tetrahydro-benzo[d]azepine-3-carboxylic acid tert-butyl ester

→

title compound

収率 61.0%

7-(5-Methyl-isoxazol-3-yl)-1,2,4,5-tetrahydro-benzo[d] azepine-3-carboxylic acid tert-butyl ester

収率 61.0%

溶媒

dichloromethane

pyridine

tetrahydrofuran

water

tetrahydrofuran

反応条件

後処理

1. 1
   その他to give an orange solution which
2. 2
   workup.STIRRINGThe mixture was stirred for 1 h
3. 3
   温度The resulting mixture was heated
4. 4
   温度to reflux for 1 h
5. 5
   その他The mixture was partitioned between dichloromethane (200 ml) and water (100 ml)
6. 6
   その他the layers separated
7. 7
   抽出The aqueous portion was extracted with dichloromethane (2×100 ml)
8. 8
   その他the combined organic extracts were evaporated
9. 9
   workup.STIRRINGthe mixture stirred for 20 min
10. 10
    洗浄washed with water (50 ml)
11. 11
    その他evaporated
12. 12
    workup.STIRRINGthe mixture stirred for 1 h
13. 13
    その他The solvent was evaporated
14. 14
    workup.DISSOLUTIONthe residue dissolved in dichloromethane (50 ml) which
15. 15
    洗浄was washed with dilute hydrochloric acid (3×50 ml, 0.5M)
16. 16
    その他The solvent was evaporated
17. 17
    その他the residue was purified by silica gel chromatography (eluent dichloromethane) which

実験手順

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%).

出典