反应详情

5,6-Dichloropyridine-3-carboxylic acid (CAS no. 41667-95-2) (32 g, 0.17 mol) was suspended in DCM (500 mL) and 1M HCl in ether (0.17 L, 0.17 mol) added. Oxalyl chloride (17 mL, 0.20 mol) and then DMF (2 drops) were added and stirred at room temperature for 16 hours. The reaction mixture was concentrated under reduced pressure, azeotroped with toluene and re-dissolved into DCM (250 mL). Azetidine hydrochloride (17.5 g, 0.18 mol) was added, followed by triethylamine (51 mL, 0.37 mol) and the reaction stirred at room temperature for 2 hours. The reaction mixture was concentrated under reduced pressure then water (500 mL) and ethyl acetate (500 mL) were added. The organic layer was separated and the aqueous phase was re-extracted with ethyl acetate (5×150 mL). The combined organics were washed with citric acid (250 mL), saturated sodium bicarbonate solution (250 mL), brine (250 mL), dried (MgSO4), filtered and evaporated under reduced pressure to give a solid which was recrystallised in ethyl acetate and dried under reduced pressure to give the product (18.2 g, 47%). 1H NMR δ (400 MHz, CDCl3) 2.34 (quintet, 2H), 4.20 (s, 2H), 4.27 (s, 2H), 8.02 (d, 1H), 8.44 (d, 1H); m/z 231 (M+H)+.

1. concentrationThe reaction mixture was concentrated under reduced pressure
2. customazeotroped with toluene
3. dissolutionre-dissolved into DCM (250 mL)
4. stirringthe reaction stirred at room temperature for 2 hours
5. concentrationThe reaction mixture was concentrated under reduced pressure
6. additionwater (500 mL) and ethyl acetate (500 mL) were added
7. customThe organic layer was separated
8. extractionthe aqueous phase was re-extracted with ethyl acetate (5×150 mL)
9. washThe combined organics were washed with citric acid (250 mL), saturated sodium bicarbonate solution (250 mL), brine (250 mL)
10. dry with materialdried (MgSO4)
11. filtrationfiltered
12. customevaporated under reduced pressure
13. customto give a solid which
14. customwas recrystallised in ethyl acetate
15. customdried under reduced pressure