Reaktion #75824

Reaktionsgleichung

tert-butyl (7bR,11aS)-6-amino-1,2,7b,10,11,11a-hexahydro-4H-pyrido[4,3-b][1,4]thiazepino[6,5,4-hi]indole-9(8H)-carboxylate

1-bromo-2,4-dichlorobenzene

NaOtBu

→

title compound

Ausbeute 61.9%

(7bR,11aS)-N-(2,4-dichlorophenyl)-1,2,7b,8,9,10,11,11a-octahydro-4H-pyrido[4,3-b][1,4]thiazepino[6,5,4-hi]indol-6-amine

Ausbeute 61.9%

Lösungsmittel

toluene

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeAn oven dried three-necked round bottom flask was fitted with septa, condenser
2. 2
   SonstigeThe solution was purged with argon at 80° C. for 25 min
3. 3
   workup.ADDITIONwere added quickly
4. 4
   TemperaturThe resulting mixture was heated to 80° C. for 20 hours under argon
5. 5
   Sonstigethe consumption of starting material by TLC (50% ethyl acetate/hexanes)
6. 6
   TemperaturAfter cooling to room temperature
7. 7
   workup.ADDITIONthe dark solution was diluted with ethyl ether (10 mL)
8. 8
   Filtrationfiltered through a pad of silica
9. 9
   Waschenwashing with ether and ethyl acetate
10. 10
    EinengenThe resulting solution was concentrated
11. 11
    Sonstigechromatographed (Combiflash, 95:5 to 75:25 hexanes/ethyl acetate gradient)

Vorschrift

An oven dried three-necked round bottom flask was fitted with septa, condenser, and a stopper. The flask was charged with tert-butyl (7bR,11aS)-6-amino-1,2,7b,10,11,11a-hexahydro-4H-pyrido[4,3-b][1,4]thiazepino[6,5,4-hi]indole-9(8H)-carboxylate (134 mg, 0.36 mmol), 1-bromo-2,4-dichlorobenzene (70 mg, 0.31 mmol), NaOtBu (60 mg, 0.62 mmol), and anhydrous toluene (5 mL). The solution was purged with argon at 80° C. for 25 min then cooled to room temperature. While maintaining a blanket of argon, Pd2(dba)3 (3.4 mg, 3.7 μmol), and BINAP (7 mg, 11.2 μmol) were added quickly. The resulting mixture was heated to 80° C. for 20 hours under argon while monitoring the consumption of starting material by TLC (50% ethyl acetate/hexanes). After cooling to room temperature, the dark solution was diluted with ethyl ether (10 mL) and filtered through a pad of silica, washing with ether and ethyl acetate. The resulting solution was concentrated and chromatographed (Combiflash, 95:5 to 75:25 hexanes/ethyl acetate gradient) yielding the title compound (78 mg, 48%) as a tan solid. 1H NMR(CDCl3, 300 MHz) δ 1.41 (s, 9H), 1.79-1.97 (m, 2H), 2.85-3.18 (m, 6H), 3.46-3.61 (m, 4H), 3.68 (s, 2H), 5.84 (s, 1H), 6.71 (d, 1H, J=1.9 Hz), 6.79 (d, 1H, J=1.8 Hz), 6.89 (d, 1H, J=8.8 Hz), 7.01 (dd, 1H, J=2.3, 8.8 Hz), 7.29 (d, 1H, J=2.3 Hz) ppm.

Quelle