Réaction #167029

Équation de réaction

pyrrolidine-1,2-dicarboxylic acid 2-[2-(7-bromo-9,10-dihydro-phenanthren-2-yl)-2-oxo-ethyl]ester 1-tert-butyl ester

tributyl(1-ethoxyvinyl)tin

NBS

2-aza-bicyclo[2.2.1]heptane-2,3-dicarboxylic acid 2-tert-butyl ester

DIPEA

→

2-aza-bicyclo[2.2.1]heptane-2,3-dicarboxylic acid 3-(2-{7-[2-(1-tert-butoxycarbonyl-pyrrolidine-2-carbonyloxy)-acetyl]-9,10-dihydro-phenanthren-2-yl}-2-oxo-ethyl)ester 2-tert-butyl ester

Solvants

ethyl acetate

dioxane

Water

ethyl acetate

acetonitrile

Conditions de réaction

Traitement

1. 1
   AutreThe reaction mixture was flushed with nitrogen
2. 2
   Températurecooled to ambient temperature
3. 3
   LavageWashed with water and brine
4. 4
   Séchagedried over Na2SO4
5. 5
   Filtrationfiltered
6. 6
   Concentrationconcentrated in vacuo
7. 7
   workup.STIRRINGThe mixture was stirred at room temperature for 16 hours
8. 8
   LavageThe organic layer was washed with NaHCO3 solution and water
9. 9
   Séchagedried over Na2SO4
10. 10
    Filtrationfiltered
11. 11
    Concentrationconcentrated in vacuo
12. 12
    AutreThe obtained residue was purified by flash chromatography

Mode opératoire

Pd(Ph3)4 (37 mg, 0.03 mmol) and PdCl2(Ph3)2 (22 mg, 0.03 mmol) were added to a mixture of pyrrolidine-1,2-dicarboxylic acid 2-[2-(7-bromo-9,10-dihydro-phenanthren-2-yl)-2-oxo-ethyl]ester 1-tert-butyl ester (410 mg, 0.8 mmol) and tributyl(1-ethoxyvinyl)tin (0.32 mL, 0.96 mmol) in 8 mL dioxane. The reaction mixture was flushed with nitrogen, heated at 80° C. for 16 hours, then cooled to ambient temperature. Water (2 mL) and NBS (171 mg, 0.96 mmol) were added and the mixture was stirred at room temperature for 40 minutes, then diluted with ethyl acetate (100 mL). Washed with water and brine, dried over Na2SO4, filtered and concentrated in vacuo. Half of the obtained residue was suspended in acetonitrile (5 mL). To it was added a solution of 2-aza-bicyclo[2.2.1]heptane-2,3-dicarboxylic acid 2-tert-butyl ester (100 mg, 0.41 mmol) and DIPEA (0.068 mL, 0.39 mmol) in 2 mL acetonitrile. The mixture was stirred at room temperature for 16 hours, then diluted with ethyl acetate (100 mL). The organic layer was washed with NaHCO3 solution and water, dried over Na2SO4, filtered and concentrated in vacuo. The obtained residue was purified by flash chromatography to provide the desired product 2-aza-bicyclo[2.2.1]heptane-2,3-dicarboxylic acid 3-(2-{7-[2-(1-tert-butoxycarbonyl-pyrrolidine-2-carbonyloxy)-acetyl]-9,10-dihydro-phenanthren-2-yl}-2-oxo-ethyl)ester 2-tert-butyl ester as a white solid (171 mg, 60% over two steps). m/z 717.2 (M+H)+.

Source