Trifluoroacetic acid → HCID 89813482, compound

HRID 2172300Notes

Reaction equation

HRID 2172300 reaction equation
Br[C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[C:4]([CH3:12])=[CH:5][N:6]=[CH:7]2.[CH3:13][O:14][C:15]1[CH:20]=[C:19]([C:21]([F:24])([F:23])[F:22])[CH:18]=[CH:17][C:16]=1B(O)O.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C(O)(C(F)(F)F)=O>O1CCOCC1.CCCCCCC.[Pt](=O)=O>[CH3:13][O:14][C:15]1[CH:20]=[C:19]([C:21]([F:22])([F:23])[F:24])[CH:18]=[CH:17][C:16]=1[C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]([CH3:12])[CH2:5][NH:6][CH2:7]2

Participants

8

Reactant 4

HCID 6422Trifluoroacetic acid2×HCID 62657Potassium Phosphate, TribasicHCID 219798825-Bromo-4-methylisoquinolineHCID 24901776(2-Methoxy-4-(trifluoromethyl)phenyl)boronic acid

Product 1

HCID 89813482HCID 89813482, compoundYield 125.1%

Reagents, catalysts & solvents 3

HCID 345198Adams' catalystCatalyst2×HCID 8900HeptaneSolventHCID 312751,4-DioxaneSolvent

Procedure

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

Workup

  1. customthe organics were separated
  2. concentrationthen concentrated
  3. dissolutionThe resulting residue was dissolved in 10 mL MeOH
  4. customwas placed under 45 psi (4559.6 kpa) H2 overnight
  5. customreaction
  6. filtrationThe reaction mixture was then filtered through diatomaceous earth
  7. additionThe filtrate was poured into saturated NaHCO3 solution
  8. extractionextracted with EtOAc
  9. dry with materialThe organics were dried over MgSO4
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-0e46f2c0beda428fb5633850d839a02a
Source dataset
uspto-grants-2015_06
Patent number
US09051311B2

Reaction notes

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