Réaction #41240

Équation de réaction

product

(3aR,6aR)-1-(4-Bromo-phenyl)-5-methyl-octahydro-pyrrolo[3,4-b]pyrrole

1-acetylpiperazine

sodium tert-butoxide

toluene

→

title compound

(3aR,6aR)-1-{4-[4-(5-Methyl-hexahydro-pyrrolo[3,4-b]pyrrol-1-yl)-phenyl]-piperazin-1-yl}-ethanone

Solvants

water

Conditions de réaction

Traitement

1. 1
   AutreThe vial was sealed
2. 2
   Extractionextracted with dichloromethane (4×)
3. 3
   LavageThe combined organic layers were washed with brine
4. 4
   Séchagedried over sodium sulfate
5. 5
   Filtrationfiltered
6. 6
   Concentrationconcentrated under reduced pressure
7. 7
   Autrepurified by column chromatography (
8. 8
   Lavageeluting with a mixture of 10% methanol and 1% ammonium hydroxide in dichloromethane)

Mode opératoire

The product of Example 7C (500 mg, 1.78 mmole), 1-acetylpiperazine (274 mg, 2.13 mmole), tris(dibenzylideneacetone)dipalladium (32.6 mg, 0.036 mmole), (r)-(+)-2,2′-bis(diphenylphosphino)-1,1′-binaphthylwere (44.3 mg, 0.071 mmole), sodium tert-butoxide (256 mg, 2.67 mmole) and 5 ml of toluene were mixed under N2 in a Emrys process vials. The vial was sealed, then heated in the microwave for 20 minutes at 150° C., using the Emrys Creator microwave reactor. The mixture was diluted with water and extracted with dichloromethane (4×). The combined organic layers were washed with brine, dried over sodium sulfate, filtered, concentrated under reduced pressure and purified by column chromatography (eluting with a mixture of 10% methanol and 1% ammonium hydroxide in dichloromethane) to provide the title compound. 1H NMR (300 MHz, CDCl3) δ ppm 6.87-6.91 (m, 2H) 6.53-6.60 (m, 2H) 4.05-4.07 (m, 1H) 3.73-3.79 (m, 2H) 3.57-3.63 (m, 2H) 3.46-3.54 (m, 1H) 3.12-3.20 (m, 1H) 2.96-3.03 (m, 4H) 2.56-2.71(m, 5H) 2.34 (s, 3H) 2.14-2.18 (m, 1H) 2.13 (s, 3H) 1.87-1.97 (m, 1H). MS: (M+H)+=329.

Source