反应详情

温度

100 °C

To a solution of 5-chloro-6-isopropoxy-nicotinic acid isopropyl ester (235 mg, 0.912 mmol) in dioxane (5 mL), 2,4,6-trimethyl-cyclotriboroxane (114 mg, 0.912 mmol), Cs2CO3 (386 mg, 1.19 mmol) and tri-tert.-butylphosphine (7.4 mg, 36 μmol) is added. The mixture is degassed and put under argon before Pd2(dba)3 (17 mg, 18 μmol) is added. The mixture is stirred at 100° C. for 18 h. The mixture is cooled to rt, diluted with water and sat. aq. NaHCO3-solution and extracted with EA. The org. extract is dried over MgSO4, filtered and concentrated. The crude product is purified on prep. TLC plates with heptane:EA 9:1 to give 6-isopropoxy-5-methyl-nicotinic acid isopropyl ester (90 mg) as a colourless oil; LC-MS: tR=1.08 min; [M+1]+=238.08; 1H NMR (CDCl3): δ 1.35-1.41 (m, 12H), 2.20 (s, 3H), 5.20-5.30 (m, 1H), 5.37-5.48 (m, 1H), 7.95 (s, 1H), 8.67 (s, 1H). The title compound can be obtained by hydrolising 6-isopropoxy-5-methyl-nicotinic acid isopropyl ester according to the procedure given in step d) of the preparation of 5,6-diisobutyl-nicotinic acid.

1. customThe mixture is degassed
2. additionis added
3. temperatureThe mixture is cooled to rt
4. extractionextracted with EA
5. extractionextract
6. dry with materialis dried over MgSO4
7. filtrationfiltered
8. concentrationconcentrated
9. customThe crude product is purified on prep