Reaktion #2259470

Reaktionsgleichung

isoquinolin-5-ylboronic acid

(n-tert-butoxycarbonyl)-1,2,3,6-tetrahydropyridine-4-boronic acid pinacol ester

1-bromo-2-iodo-4-(trifluoromethyl)benzene

potassium phosphate

tert-butyl 4-(2-bromo-5-(trifluoromethyl)phenyl)-5,6-dihydropyridine-1(2H)-carboxylate

→

tert-butyl 4-(2-(isoquinolin-5-yl)-5-(trifluoromethyl)phenyl)-5,6-dihydropyridine-1(2H)-carboxylate

Lösungsmittel

dioxane

water

diethyl ether

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturto cool to room temperature
2. 2
   WaschenThe organics were washed with water
3. 3
   Trocknenbrine, dried over MgSO4
4. 4
   Einengenconcentrated
5. 5
   SonstigePurification of the resulting residue by silica gel column chromatography (0 to 100% EtOAc/heptane)

Vorschrift

A solution of Cl2Pd(dppf)-CH2Cl2 adduct (Strem Chemicals Inc., Newburyport, Mass., 1.157 g, 1.416 mmol), (n-tert-butoxycarbonyl)-1,2,3,6-tetrahydropyridine-4-boronic acid pinacol ester (Maybridge Chemicals, Cornwall, UK, 8.76 ml, 28.3 mmol), 1-bromo-2-iodo-4-(trifluoromethyl)benzene (Combi-Blocks, San Diego, Calif., 9.94 g, 28.3 mmol), and potassium phosphate (36.1 g, 170 mmol) in 100 mL dioxane and 40 mL water was heated to 100° C. for 3 hours. LC/MS showed clean conversion to tert-butyl 4-(2-bromo-5-(trifluoromethyl)phenyl)-5,6-dihydropyridine-1(2H)-carboxylate. To the resulting mixture was added isoquinolin-5-ylboronic acid (Sigma-Aldrich, St. Louis, Mo., 4.90 g, 28.3 mmol) and Cl2Pd(AmPhos) (Sigma-Aldrich, St. Louis, Mo., 1.003 g, 1.416 mmol). The reaction mixture was again heated to 100° C. an additional hour before the reaction mixture was allowed to cool to room temperature and was diluted with diethyl ether. The organics were washed with water, then brine, dried over MgSO4 and concentrated. Purification of the resulting residue by silica gel column chromatography (0 to 100% EtOAc/heptane) gave tert-butyl 4-(2-(isoquinolin-5-yl)-5-(trifluoromethyl)phenyl)-5,6-dihydropyridine-1(2H)-carboxylate (9.80 g, 21.56 mmol).

Quelle