Phosgene → 4-(3-Cyclobutyl-2,3,4,5-tetrahydro-1h-benzo[d]azepin-7-yloxy)-piperidine-1-carboxylic acid diethylamide

3-Cyclobutyl-7-(piperidin-4-yloxy)-2,3,4,5-tetrahydro-1H-benzo[d]azepine (E6) (1.5 g, 5 mmol) dissolved in toluene (40 ml) was added slowly to a 20% phosgene in toluene solution (12.5 ml, 25 mmol) at 0° C. The mixture was stirred at room temperature for 3 hours and concentrated in vacuo to afford a crude residue (1.91 g). The crude product (300 mg, 0.75 mmol) was then added to a stirred slurry of diethylamine (207 μL, 2 mmol) and diethylaminomethyl polystyrene (3.2 mmol/g, 1.41 g, 4.5 mmol) in dichloromethane (10 ml). The reaction mixture was stirred at room temperature for 16 hours, filtered and concentrated in vacuo. The crude residue was purified by column chromatography eluting with dichloromethane then a mixture of 0.880 ammonia:ethanol:dichloromethane (1:9:90) to afford the title product (E61). MS (ES+) m/e 400 [M+H]+.

1. concentrationconcentrated in vacuo
2. customto afford a crude residue (1.91 g)
3. stirringThe reaction mixture was stirred at room temperature for 16 hours
4. filtrationfiltered
5. concentrationconcentrated in vacuo
6. customThe crude residue was purified by column chromatography
7. washeluting with dichloromethane
8. additiona mixture of 0.880 ammonia:ethanol:dichloromethane (1:9:90)

ORD-Eintrag

ord-bec5eb090e694919833b8d2649a7a8b3

Quelldatensatz

uspto-grants-2012_06

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08207331B2