Acetic Acid → Isoquinoline, 1,2,3,4-tetrahydro-5-[2-(1H-imidazol-1-yl)-4-(trifluoromethyl)phenyl]-

HRID 2172297Notes

Reaction equation

HRID 2172297 reaction equation
[CH:1]1[C:10]2[C:5](=[C:6](B(O)O)[CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][N:2]=1.Br[C:15]1[CH:20]=[CH:19][C:18]([C:21]([F:24])([F:23])[F:22])=[CH:17][C:16]=1[N:25]1[CH:29]=[CH:28][N:27]=[CH:26]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C(O)(=O)C>O1CCOCC1.C(OCC)C.[Pt](=O)=O>[N:25]1([C:16]2[CH:17]=[C:18]([C:21]([F:22])([F:23])[F:24])[CH:19]=[CH:20][C:15]=2[C:6]2[CH:7]=[CH:8][CH:9]=[C:10]3[C:5]=2[CH2:4][CH2:3][NH:2][CH2:1]3)[CH:29]=[CH:28][N:27]=[CH:26]1

Participants

8

Reactant 4

HCID 176Acetic AcidHCID 62657Potassium Phosphate, TribasicHCID 599474Isoquinoline-5-boronic acidHCID 86687409HCID 86687409, compound

Product 1

HCID 89815434Isoquinoline, 1,2,3,4-tetrahydro-5-[2-(1H-imidazol-1-yl)-4-(trifluoromethyl)phenyl]-Yield 95.4%

Reagents, catalysts & solvents 3

HCID 345198Adams' catalystCatalystHCID 3283Diethyl EtherSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of Cl2Pd(AmPhos) (Sigma-Aldrich, St. Louis, Mo., 0.049 g, 0.069 mmol), isoquinolin-5-ylboronic acid (Frontier Scientific, Logan, Utah, 0.297 g, 1.718 mmol), 1-(2-bromo-5-(trifluoromethyl)phenyl)-1H-imidazole (0.400 g, 1.374 mmol), and potassium phosphate (1.167 g, 5.50 mmol) in 6 mL dioxane 3 mL water was heated to 120° C. overnight. The reaction mixture was diluted with diethyl ether. The organics were separated and concentrated. The resulting residue was taken up in 6 mL MeOH, was treated with platinum(IV) oxide (0.031 g, 0.137 mmol) and acetic acid (0.236 ml, 4.12 mmol) and was placed under 45 psi (4559.6 kpa) H2 for 2 hours. The reaction mixture was filtered through a plug of diatomaceous earth eluting with EtOAc. The filtrate was washed with saturated NaHCO3 solution, the organics dried over MgSO4 and concentrated yielding 5-(2-(1H-imidazol-1-yl)-4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydroisoquinoline (0.450 g, 1.311 mmol). [M+H]+=344.0

Workup

  1. customThe organics were separated
  2. concentrationconcentrated
  3. filtrationThe reaction mixture was filtered through a plug of diatomaceous earth
  4. washeluting with EtOAc
  5. washThe filtrate was washed with saturated NaHCO3 solution
  6. dry with materialthe organics dried over MgSO4
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-05df0d2455c64a9089ca476c0ee99641
Source dataset
uspto-grants-2015_06
Patent number
US09051311B2

Reaction notes

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