Reaktion #2266614

Reaktionsgleichung

product

ethyl 7-chloro-9-(phenylsulfonyl)-4,5-dihydro-1H-benzofuro[2,3-d]azepine-3(2H)-carboxylate

KOH

HCl

→

7-chloro-9-(phenylsulfonyl)-2,3,4,5-tetrahydro-1H-benzofuro[2,3-d]azepine hydrochloride

Ausbeute 31.4%

Lösungsmittel

water

ethylene glycol

DME

methanol

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturAfter cooling to ambient temperature
2. 2
   Extraktionextracted with dichloromethane (3×20 mL)
3. 3
   WaschenThe combined organic extracts were washed with brine
4. 4
   Trocknendried over Na2SO4
5. 5
   Filtrationfiltered
6. 6
   Einengenconcentrated in vacuo
7. 7
   SonstigeThe crude product was purified by semi-preparative HPLC
8. 8
   Sonstigeto give the free base which
9. 9
   EinengenConcentration in vacuo

Vorschrift

The product of step E (35 mg, 0.08 mmol) was dissolved in a mixture of ethylene glycol (0.5 mL) and DME (0.5 mL) then treated with 20% KOH solution (0.5 mL). The reaction mixture was heated to 100° C. for 36 h. After cooling to ambient temperature, the reaction mixture was diluted with water (5 mL) and extracted with dichloromethane (3×20 mL). The combined organic extracts were washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was purified by semi-preparative HPLC to give the free base which was treated directly with 1.25 M HCl in methanol solution. Concentration in vacuo afforded 7-chloro-9-(phenylsulfonyl)-2,3,4,5-tetrahydro-1H-benzofuro[2,3-d]azepine hydrochloride (5 mg, 15%, AUC HPLC>99%) as a white solid: 1H NMR (CD3OD, 300 MHz) δ 8.18 (d, J=2.0 Hz, 1H), 8.00 (d, J=7.4 Hz, 2H), 7.90 (d, J=1.7 Hz, 1H), 7.68-7.52 (m, 3H), 3.60-3.51 (m, 4H), 3.42-3.35 (m, 2H), 3.23-3.15 (m, 2H); APCI MS m/z 362 [M+H]+.

Quelle