Citric Acid → HCID 22329270, Verbindung

Temperatur

-15 °C

In THF (150 ml) was dissolved methyl 7-bromo-1-(t-butoxycarbonyl)-1,2,3,4-tetrahydro-1-benzazepin-5-one-4-carboxylate (7.2 g). To the solution was added sodium borohydride (0.7 g) at −40° C., and then was added dropwise methanol (15 ml). The mixture was stirred at −15° C. for 1 hour. To the mixture was added 1M citric acid, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine and dried with anhydrous magnesium sulfate, and the solvent was evaporated. The residue was dissolved in THF (150 ml), and to the solution was added triethylamine (7.5 ml). To the mixture was added dropwise, under ice-cooling, methanesulfonyl chloride (2.1 ml). Under nitrogen atmosphere, the mixture was stirred at room temperature for 1.5 hours, and to the mixture was added dropwise DBU (13.5 ml) at room temperature. The mixture was stirred at 90° C. for 10 minutes, and the solvent was evaporated. To the residue was added water, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine and dried with anhydrous magnesium sulfate, and the solvent was evaporated. The residue was purified with silica gel column chromatography (ethyl acetate/hexane) to give methyl 7-bromo-1-(t-butoxycarbonyl)-2,3-dihydro-1H-1-benzazepine-4-carboxylate (5.18 g) as colorless crystals.

1. extractionthe mixture was extracted with ethyl acetate
2. washThe organic layer was washed with water and saturated brine
3. dry with materialdried with anhydrous magnesium sulfate
4. customthe solvent was evaporated
5. dissolutionThe residue was dissolved in THF (150 ml)
6. additionto the solution was added triethylamine (7.5 ml)
7. additionTo the mixture was added dropwise, under ice-
8. temperaturecooling
9. stirringUnder nitrogen atmosphere, the mixture was stirred at room temperature for 1.5 hours
10. additionto the mixture was added dropwise DBU (13.5 ml) at room temperature
11. stirringThe mixture was stirred at 90° C. for 10 minutes
12. customthe solvent was evaporated
13. additionTo the residue was added water
14. extractionthe mixture was extracted with ethyl acetate
15. washThe organic layer was washed with water and saturated brine
16. dry with materialdried with anhydrous magnesium sulfate
17. customthe solvent was evaporated
18. customThe residue was purified with silica gel column chromatography (ethyl acetate/hexane)

ORD-Eintrag

ord-37593cb58a614e13ac0dbecdefa6de27

Quelldatensatz

uspto-grants-2005_08

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US06936602B1