反应详情

9-borabicyclo[3.3.1]nonane (101.5 ml of a 0.5M solution in tetrahydrofuran) was added to a degassed sample of N-(tert-butoxycarbonyl)-4-methylene piperidine (may be prepared as described in A. Palani et al., J. Med. Chem., 2002, 45: 3145) (10 g) and the resultant solution heated at reflux for 1 h. After cooling to room temperature the reaction mixture was then added to a mixture of 4-bromopyridine (7.23 g), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (1:1) (1.14 g), K2CO3 (8.42 g), N,N-dimethylformamide (100 ml) and water (10 ml), and the resultant mixture heated at 60° C. for 3 h. After cooling to room temperature, another charge of [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (1:1) (1.14 g) was added to the reaction and heated at 60° C. overnight. The mixture was cooled to room temperature and poured into water, the pH was adjusted to 11 by the addition of 10% aqueous sodium hydroxide and extracted into ethyl acetate. Combined organic extracts were dried (Na2SO4) and evaporated to give the crude pyridine as a brown viscous oil. Chromatography [silica gel, eluting with ethyl acetate in hexanes, 0-100%] gave the title compound (D1) as a pale yellow oil (7.5 g).

1. custommay be prepared
2. temperatureat reflux for 1 h
3. temperatureAfter cooling to room temperature
4. additionwas added to the reaction
5. temperatureheated at 60° C. overnight
6. temperatureThe mixture was cooled to room temperature
7. extractionextracted into ethyl acetate
8. dry with materialCombined organic extracts were dried (Na2SO4)
9. customevaporated
10. customto give the crude pyridine as a brown viscous oil
11. washChromatography [silica gel, eluting with ethyl acetate in hexanes, 0-100%]