1.81 g |
|
Intermediate X: 5-(2-Methoxy-4-(trifluoromethyl)phenyl)-4-methyl-l, 2,3,4- tetrahydroisoquinoline A solution of Cl2Pd(AmPhos) (Sigma-Aldrich, St. Louis, MO, 0.319 g, 0.450 mmol), <strong>[651310-24-6]5-bromo-4-methylisoquinoline</strong> (Frontier Scientific, Logan, UT, 1.000 g, 4.50 mmol), (2-methoxy-4-(trifluoromethyl)phenyl)boronic acid (Combi-Blocks, San Diego, CA, 0.990 g, 4.50 mmol), and potassium phosphate (3.82 g, 18.01 mmol) in 10 mL dioxane 5 mL water was heated to 80C for overnight. The reaction mixture was diluted with heptane, and the organics were separated then concentrated. The resulting residue was dissolved in 10 mL MeOH, was treated with platinum(IV) oxide (0.102 g, 0.450 mmol) and TFA (0.694 ml, 9.01 mmol) and was placed under 45psi (4559.6 kpa) H2 overnight. LC/MS showed incomplete reaction, so an additional portion of platinum(IV) oxide (0.102 g, 0.450 mmol) and TFA (0.694 ml, 9.01 mmol) were added, and the reaction mixture was placed under 45psi (4559.6 kpa) H2 for an additional 6 hours. The reaction mixture was then filtered through diatomaceous earth. The filtrate was poured into saturated aHC03 solution and extracted with EtOAc. The organics were dried over MgS04 and concentrated yielding racemic 5-(2- methoxy-4-(trifluoromethyl)phenyl)-4-methyl- 1 ,2,3 ,4-tetrahydroisoquinoline (1.810 g, 5.63 mmol). [M+H]+ = 322.2 |