Reaktion #2259482

Reaktionsgleichung

potassium phosphate

5-bromo-4-methylisoquinoline

(2-methoxy-4-(trifluoromethyl)phenyl)boronic acid

TFA

TFA

→

racemic 5-(2-methoxy-4-(trifluoromethyl)phenyl)-4-methyl-1,2,3,4-tetrahydroisoquinoline

Ausbeute 125.1%

Lösungsmittel

dioxane

heptane

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigethe organics were separated
2. 2
   Einengenthen concentrated
3. 3
   workup.DISSOLUTIONThe resulting residue was dissolved in 10 mL MeOH
4. 4
   Sonstigewas placed under 45 psi (4559.6 kpa) H2 overnight
5. 5
   Sonstigereaction
6. 6
   FiltrationThe reaction mixture was then filtered through diatomaceous earth
7. 7
   workup.ADDITIONThe filtrate was poured into saturated NaHCO3 solution
8. 8
   Extraktionextracted with EtOAc
9. 9
   TrocknenThe organics were dried over MgSO4
10. 10
    Einengenconcentrated

Vorschrift

A solution of Cl2Pd(AmPhos) (Sigma-Aldrich, St. Louis, Mo., 0.319 g, 0.450 mmol), 5-bromo-4-methylisoquinoline (Frontier Scientific, Logan, Utah, 1.000 g, 4.50 mmol), (2-methoxy-4-(trifluoromethyl)phenyl)boronic acid (Combi-Blocks, San Diego, Calif., 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 80° C. 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 45 psi (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 45 psi (4559.6 kpa) H2 for an additional 6 hours. The reaction mixture was then filtered through diatomaceous earth. The filtrate was poured into saturated NaHCO3 solution and extracted with EtOAc. The organics were dried over MgSO4 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

Quelle