反应详情

To a mixture of tert-butyl 4-{[(trifluoromethyl)sulfonyl]oxy}-3,6-dihydropyridine-1(2H)-carboxylate (prepared according to Wustrow, D. J., Wise, L. D., Synthesis, (1991), 993-995; 3.24 g, 9.77 mmol), 3-cyanophenylboronic acid (2.01 g, 13.7 mmol), lithium chloride (1.23 g, 29.3 mmol), and 2 M Na2CO3 solution (14 mL) in DME (35 mL) was added Pd(PPh3)4 (564 mg, 0.489 mmol), and the resulting mixture was stirred at reflux under a nitrogen atmosphere for 3.5 h. The reaction mixture was cooled to rt, stirred overnight, then partially concentrated to remove most of the DME. To the remaining aqueous mixture was added DCM, 2M Na2CO3 solution, and ˜6 mL of 28% NH4OH solution. The layers were separated and the aqueous layer was extracted again with DCM. The combined organic layers were dried over anhydrous MgSO4, filtered, and concentrated. Purification by MPLC (silica, 45% ethyl acetate/hexanes eluent) afforded tert-butyl 4-(3-cyanophenyl)-3,6-dihydropyridine-1(2H)-carboxylate. 1HNMR (CDCl3, 500 MHz): δ 7.66 (s, 1H), 7.61 (dd, J=8.0, 1.5 Hz, 1H), 7.56 (d, J=8.0 Hz, 1H), 7.46 (t, J=7.5 Hz, 1H), 6.13 (br s, 1H), 4.12 (m, 2H), 3.68 (t, J=5.5 Hz, 2H), 2.53 (br s, 2H), 1.52 (s, 9H).

1. customprepared
2. custom, Synthesis, (1991), 993-995
3. temperatureat reflux under a nitrogen atmosphere for 3.5 h
4. stirringstirred overnight
5. concentrationpartially concentrated
6. customto remove most of the DME
7. additionTo the remaining aqueous mixture was added DCM, 2M Na2CO3 solution, and ˜6 mL of 28% NH4OH solution
8. customThe layers were separated
9. extractionthe aqueous layer was extracted again with DCM
10. dry with materialThe combined organic layers were dried over anhydrous MgSO4
11. filtrationfiltered
12. concentrationconcentrated
13. customPurification by MPLC (silica, 45% ethyl acetate/hexanes eluent)