反应详情

Sodium Hydride (60 wt % dispersion in mineral oil, 6.36 g, 0.156 mol) was added in portions to a solution of 1-benzhydryl-azetidin-3-ol (25.38 g, 0.106 mol) in anhydrous dimethylformamide (400 mL) under a Nitrogen atmosphere. This caused a precipitate to form and effervescence to occur. When addition was complete the reaction mixture was stirred at ambient temperature for 15 min. A solution of 2-chloro-5-iodopyridine (25.40 g, 0.106 mol) in dimethylformamide (100 mL) was added to the reaction mixture via a dropping funnel over 15 minutes. When addition was complete the reaction mixture was heated to 70° C. and stirred, under nitrogen atmosphere, for 4.5 hr. Reaction mixture was then allowed to cool to ambient temperature and a sat. aqueous ammonium chloride solution (30 mL) was added. The solvents were removed in vacuo and the residual solid was partitioned between ethyl acetate (600 mL) and sat. aqueous sodium bicarbonate solution (500 mL). The phases were separated and the organic phase was washed with sat. aqueous sodium chloride solution (3×300 mL), dried over sodium sulphate, filtered and filtrate solvents removed in vacuo to afford a yellow-brown solid which was triturated with diethyl ether, filtered and dried in vacuo to afford the title compound as a beige-coloured solid (33.41 g, 71%)

1. customto form
2. additionWhen addition
3. additionWhen addition
4. temperaturewas heated to 70° C.
5. stirringstirred, under nitrogen atmosphere, for 4.5 hr
6. customReaction mixture
7. temperatureto cool to ambient temperature
8. customThe solvents were removed in vacuo
9. customthe residual solid was partitioned between ethyl acetate (600 mL) and sat. aqueous sodium bicarbonate solution (500 mL)
10. customThe phases were separated
11. washthe organic phase was washed with sat. aqueous sodium chloride solution (3×300 mL)
12. dry with materialdried over sodium sulphate
13. filtrationfiltered
14. customfiltrate solvents removed in vacuo
15. customto afford a yellow-brown solid which
16. customwas triturated with diethyl ether
17. filtrationfiltered
18. customdried in vacuo