Reaction #157314

Reaction equation

Sodium hydroxide

9-Borabicyclo[3.3.1]nonane

1-benzyl 4-tert-butyl 2-vinylpiperazine-1,4-dicarboxylate

3-bromopyridine

triphenylphosphine

→

desired product

Yield 63.0%

1-benzyl 4-tert-butyl 2-(2-(pyridin-3-yl)ethyl)piperazine-1,4-dicarboxylate

Yield 63.0%

Conditions

Workup

1. 1
   OtherOnce bubbling
2. 2
   Temperaturethe reaction mixture was heated
3. 3
   Temperatureto reflux overnight
4. 4
   workup.ADDITIONthe reaction mixture was diluted with water (200 mL)
5. 5
   Extractionextracted with EtOAc (3×200 mL)
6. 6
   DryingThe combined organics were dried over Na2SO4
7. 7
   Filtrationfiltered
8. 8
   Concentrationconcentrated under reduced pressure
9. 9
   OtherPurification by column chomatography (10 to 40% EtOAc in Hexane gradient)

Procedure

9-Borabicyclo[3.3.1]nonane (0.5M solution in THF, 54 mL, 27 mmol) was added to 1-benzyl 4-tert-butyl 2-vinylpiperazine-1,4-dicarboxylate (2.33 g, 6.73 mmol). After 3 h, 3-bromopyridine (0.99 mL, 10.1 mmol), triphenylphosphine (0.53 g, 2.0 mmol), and tetrakis(triphenylphosphine) palladium(0) (0.311 g, 0.27 mmol) were added. Sodium hydroxide (1N aqueous solution, 16.8 mL, 16.8 mmol) was added slowly. Once bubbling ceased, the reaction mixture was heated to reflux overnight. Upon cooling to rt, the reaction mixture was diluted with water (200 mL) and extracted with EtOAc (3×200 mL). The combined organics were dried over Na2SO4, filtered, and concentrated under reduced pressure. Purification by column chomatography (10 to 40% EtOAc in Hexane gradient) gave 1.79 g (63%) of the desired product as a thick oil. Rf=0.57 in 80% EtOAc/Hexane. LC-MS: RT=7.69 min., [M+H]+=426.2. The material was contaminated with ˜15% triphenylphosphine, and was used without further purification.

Source