Trifluoroacetic acid → 9-Bromo-3,4,7,8-tetrahydro-[1,4]diazepino[7,1-a]isoquinoline-2,5-dione

methyl 2-(2-acetyl-5-bromo-1,2,3,4-tetrahydroisoquinolin-1-yl)acetate. A stirred solution of methyl 2-(2-acetyl-5-bromo-1,2-dihydroisoquinolin-1-yl)acetate (147 g, 453 mmol), triethylsilane (388 g, 3333 mmol) and trifluoroacetic acid (266 mL, 3446 mmol) in 1,2-dichloroethane (1100 mL) was stirred at 80° C. for 3 h. The reaction mixture was cooled to rt and the solvent was evaporated under reduced pressure. The remaining volatile components were evaporated under high vacuo and 40° C. bath temperature. To the resulting yellow residue saturated aqueous NaHCO3 (500 mL) was added while stirring and the mixture was extracted with DCM (3×400 mL). The organic layer was washed with saturated aqueous NaHCO3 (300 mL) and brine (300 mL). The organic layer was treated with charcoal, then dried with sodium sulfate, filtered through a pad of Hyflo and the solvent was removed under reduced pressure. The crude product was crystallized from diethyl ether (300 mL) to yield the title compound as white crystals (90 g). UPLC-MS: MS 326.0/328.0 (M+H+); UPLC rt 0.94 min.

1. customthe solvent was evaporated under reduced pressure
2. customThe remaining volatile components were evaporated under high vacuo and 40° C. bath temperature
3. additionTo the resulting yellow residue saturated aqueous NaHCO3 (500 mL) was added
4. extractionthe mixture was extracted with DCM (3×400 mL)
5. washThe organic layer was washed with saturated aqueous NaHCO3 (300 mL) and brine (300 mL)
6. additionThe organic layer was treated with charcoal
7. dry with materialdried with sodium sulfate
8. filtrationfiltered through a pad of Hyflo
9. customthe solvent was removed under reduced pressure
10. customThe crude product was crystallized from diethyl ether (300 mL)

ORD record

ord-64026e0ee03c4da28982e7a1dc4eb296

Source dataset

uspto-grants-2014_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08853203B2