反应详情

Oxalyl chloride (3.2 mL; 36.0 mmol) was added to a solution of 5,6 dichloronicotinic acid (5.76 g; 30.0 mmol) and 4M hydrogen chloride in dioxan (7.5 mL; 30.0 mmol) in DCM (50 mL). The mixture was stirred at RT for 18 hours, the DCM evaporated in vacuo, the residue azeotroped with toluene (2×15 mL) then added to a solution of pyrrolidine (3.0 mL; 36.0 mmol) and triethylamine (10.0 mL; 72 mmol) in DCM (150 mL). The mixture was stirred at RT for 6 hours, the DCM evaporated in vacuo, the residue partitioned between water (75 mL) and ethyl acetate (100 mL), the organic layer washed with brine, dried (MgSO4) and evaporated in vacuo. The residue was chromatographed on silica, eluting with 50% ethyl acetate in isohexane, to give the desired compound which was further purified by crystallisation from ethyl acetate and isohexane (6.88 g). 1H NMR δ (CDCl3): 1.9 (m, 4H), 3.4 (m, 2H), 3.6 (s, 3H), 7.9 (s, 1H) and 8.4 (s, 1H); m/z 245 (M+H)+.

1. customthe DCM evaporated in vacuo
2. customthe residue azeotroped with toluene (2×15 mL)
3. stirringThe mixture was stirred at RT for 6 hours
4. customthe DCM evaporated in vacuo
5. customthe residue partitioned between water (75 mL) and ethyl acetate (100 mL)
6. washthe organic layer washed with brine
7. dry with materialdried (MgSO4)
8. customevaporated in vacuo
9. customThe residue was chromatographed on silica
10. washeluting with 50% ethyl acetate in isohexane