反应详情

Oxalyl chloride (1.01 mL, 11.6 mmol) was added to a suspension of 4-chloronicotinic acid (prepared according to F. Guillier et al. J. Org. Chem. 1995, 60, 292) (1.5 g, 7.7 mmol) in CH2Cl2 (15 mL) containing 2 drops of DMF. The mixture was stirred at room temperature for 1 h then evaporated to dryness, suspended in CH2Cl2 (10 mL) and re-evaporated. The residue was re-suspended in CH2Cl2 (10 mL), cooled to 0° C. and treated with triethylamine (3.23 mL, 23.2 mmol) dropwise followed by a 2M solution of methylamine in THF (7.7 mL, 15.4 mmol) dropwise. The resulting orange mixture was stirred at 0° C. for 20 min before being concentrated in vacuo. The residue was treated with sat. NaHCO3 (aq) (30 mL), extracted with CH2Cl2 10×25 mL) and the combined organic layers were dried (MgSO4) and evaporated to give an orange oil which crystallised. The solid was triturated with ether (10 mL), stirred for 30 min, then filtered and washed with 1:1 ether/pentane (20 mL) to give the title amide (986 mg, 75%) as an off-white solid; δH (CDCl3, 400 MHz) 3.07 (3H, d), 6.20 (1H, br), 7.37 (1H, d), 8.53 (1H, d), 8.86 (1H, s).

1. customthen evaporated to dryness
2. customre-evaporated
3. temperaturecooled to 0° C.
4. stirringThe resulting orange mixture was stirred at 0° C. for 20 min
5. concentrationbefore being concentrated in vacuo
6. additionThe residue was treated with sat. NaHCO3 (aq) (30 mL)
7. extractionextracted with CH2Cl2 10×25 mL) and the combined organic layers
8. dry with materialwere dried (MgSO4)
9. customevaporated
10. customto give an orange oil which
11. customcrystallised
12. customThe solid was triturated with ether (10 mL)
13. stirringstirred for 30 min
14. filtrationfiltered
15. washwashed with 1:1 ether/pentane (20 mL)