تفاعل #167029

معادلة التفاعل

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

المذيبات

ethyl acetate

dioxane

Water

ethyl acetate

acetonitrile

ظروف التفاعل

المعالجة

1. 1
   أخرىThe reaction mixture was flushed with nitrogen
2. 2
   درجة الحرارةcooled to ambient temperature
3. 3
   غسيلWashed with water and brine
4. 4
   تجفيفdried over Na2SO4
5. 5
   ترشيحfiltered
6. 6
   تركيزconcentrated in vacuo
7. 7
   workup.STIRRINGThe mixture was stirred at room temperature for 16 hours
8. 8
   غسيلThe organic layer was washed with NaHCO3 solution and water
9. 9
   تجفيفdried over Na2SO4
10. 10
    ترشيحfiltered
11. 11
    تركيزconcentrated in vacuo
12. 12
    أخرىThe obtained residue was purified by flash chromatography

الإجراء التجريبي

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)+.

المصدر