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

HRID 926251Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 926251
BrC1C=CC=C2C=1CC[NH:6]C2CC(OC)=O.S(=O)(=O)(O)O.[C:22]([N:25]1[CH2:34][CH2:33][C:32]2[C:27](=[CH:28][CH:29]=[CH:30][C:31]=2[Br:35])[CH:26]1[CH2:36][C:37]([O:39]C)=O)(=[O:24])[CH3:23].C([O-])(O)=O.[Na+]>O.CO>[Br:35][C:31]1[CH:30]=[CH:29][CH:28]=[C:27]2[C:32]=1[CH2:33][CH2:34][N:25]1[C:22](=[O:24])[CH2:23][NH:6][C:37](=[O:39])[CH:36]=[C:26]12

Komponenten

7

Edukt 4

HCID 1118Sulfuric AcidHCID 516892Sodium BicarbonateHCID 86711329Methyl 2-(5-bromo-1,2,3,4-tetrahydroisoquinolin-1-yl)acetateHCID 89980026Methyl 2-(2-acetyl-5-bromo-1,2,3,4-tetrahydroisoquinolin-1-yl)acetate

Produkt 1

HCID 867113289-Bromo-3,4,7,8-tetrahydro-[1,4]diazepino[7,1-a]isoquinoline-2,5-dione

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 887MethanolLösungsmittelHCID 962WaterLösungsmittel

Versuchsvorschrift

methyl 2-(5-bromo-1,2,3,4-tetrahydroisoquinolin-1-yl)acetate. MeOH (1280 mL) was cooled to −15° C. and conc. Sulfuric acid (147 mL, 2759 mmol) was added slowly (exotherm) under cooling. To this solution, methyl 2-(2-acetyl-5-bromo-1,2,3,4-tetrahydroisoquinolin-1-yl)acetate (90 g, 276 mmol) was added and the reaction mixture was stirred under reflux for 96 h. The reaction mixture was cooled to RT and slowly added to a solution of NaHCO3 (540 g) in water (1.35 L). The slightly basic aqueous solution was extracted with AcOEt (3×500 mL). The combined organic layers were washed with saturated aqueous NaHCO3 (300 mL) and brine (300 mL). The organic layer was dried with sodium sulfate, filtered and the solvent was removed under reduced pressure. The crude product was dried under high vacuo to yield the title compound as yellow foam (76 g) which was used without further purification. UPLC-MS: MS 284.1/286.1 (M+H+); UPLC rt 0.50 min.

Aufarbeitung

  1. temperatureunder cooling
  2. temperatureunder reflux for 96 h
  3. extractionThe slightly basic aqueous solution was extracted with AcOEt (3×500 mL)
  4. washThe combined organic layers were washed with saturated aqueous NaHCO3 (300 mL) and brine (300 mL)
  5. dry with materialThe organic layer was dried with sodium sulfate
  6. filtrationfiltered
  7. customthe solvent was removed under reduced pressure
  8. dry with materialThe crude product was dried under high vacuo

Quellen und Nachweise

ORD-Eintrag
ord-9785ec2fcfa842519a51211802ade56d
Quelldatensatz
uspto-grants-2016_03
Patentnummer
US09284331B2

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