Trifluoroacetonitrile → HCID 178487749, compound

HRID 1852151Notes

Reaction equation

HRID 1852151 reaction equation
C(N(CC)[C:4](=[O:14])[C:5]1[CH:10]=[CH:9][C:8]([O:11][CH3:12])=[CH:7][C:6]=1[CH3:13])C.C([Li])(C)(C)C.[F:22][C:23]([F:27])([F:26])[C:24]#[N:25]>C1COCC1>[CH3:12][O:11][C:8]1[CH:7]=[C:6]2[C:5](=[CH:10][CH:9]=1)[C:4]([OH:14])=[N:25][C:24]([C:23]([F:27])([F:26])[F:22])=[CH:13]2

Participants

5

Reactant 3

HCID 67710TrifluoroacetonitrileHCID 11053218N,N-diethyl-4-methoxy-2-methyl-benzamideHCID 178418306HCID 178418306, compound

Product 1

HCID 178487749HCID 178487749, compoundYield 24.66%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of N,N-diethyl-4-methoxy-2-methylbenzamide (1 g, 4.52 mmol) in THF (40 mL) was added tert-butyllithium (3.99 mL, 6.78 mmol) dropwise at −78° C. After stirring for 0.5 h, 2,2,2-trifluoroacetonitrile (0.472 g, 4.97 mmol) was bubbled through the solution via syringe for 1 minute, then warmed to rt, and stirred for 16 h. The reaction mixture was quenched with water (1 mL) and partially evaporated to half to one third of original volume, neutralized with 1 N HCl. The solution was separated with EtOAc. The organics were collected, washed with brine, dried over MgSO4, filtered and evaporated to give crude material as a dark yellow solid. The crude material was purified via silica gel chromatography (90 g column, 10-50% EtOAc:Hex) to give the product 6-methoxy-3-(trifluoromethyl)isoquinolin-1-ol (271 mg, 1.114 mmol, 24.66% yield) as a light yellow solid. MS: MS m/z 244.19(M++1).

Workup

  1. stirringstirred for 16 h
  2. customThe reaction mixture was quenched with water (1 mL)
  3. custompartially evaporated to half to one third of original volume
  4. customThe solution was separated with EtOAc
  5. customThe organics were collected
  6. washwashed with brine
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. customevaporated
  10. customto give crude material as a dark yellow solid
  11. customThe crude material was purified via silica gel chromatography (90 g column, 10-50% EtOAc:Hex)

Sources & evidence

ORD record
ord-4ccbc705d7fc4ab5a88f016c2d63dd95
Source dataset
uspto-grants-2015_02
Patent number
US08957203B2

Reaction notes

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