3-(Trifluoromethyl)benzaldehyde → (+/-)-2-Methoxy-alpha-[3-(trifluoromethyl)phenyl]-6-quinoline methanol

HRID 581998Notes

Reaction equation

HRID 581998 reaction equation
C([Li])CCC.Br[C:7]1[CH:8]=[C:9]2[C:14](=[CH:15][CH:16]=1)[N:13]=[C:12]([O:17][CH3:18])[CH:11]=[CH:10]2.[F:19][C:20]([F:30])([F:29])[C:21]1[CH:22]=[C:23]([CH:26]=[CH:27][CH:28]=1)[CH:24]=[O:25]>O1CCCC1>[CH3:18][O:17][C:12]1[CH:11]=[CH:10][C:9]2[C:14](=[CH:15][CH:16]=[C:7]([CH:24]([C:23]3[CH:26]=[CH:27][CH:28]=[C:21]([C:20]([F:19])([F:29])[F:30])[CH:22]=3)[OH:25])[CH:8]=2)[N:13]=1

Participants

5

Reactant 3

HCID 679903-(Trifluoromethyl)benzaldehydeHCID 106575386-Bromo-2-methoxyquinolineHCID 178418339Butyllithium

Product 1

HCID 54187627(+/-)-2-Methoxy-alpha-[3-(trifluoromethyl)phenyl]-6-quinoline methanolYield 66.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

Butyllithium (12.5 ml) was added dropwise at -78° C. to a solution of 6-bromo-2-methoxyquinoline (4 g) in tetrahydrofuran (160 ml). After complete addition the mixture was stirred at -78° C. for 15 minutes. A solution of 3-(trifluoromethyl)-benzaldehyde (3.51 g) in tetrahydrofuran (40 ml) was added dropwise and the mixture was stirred at -78° C. for 30 minutes, then quenched with water (50 ml) and extracted with ethylacetate. The organic layer was separated, washed with brine, dried over MgSO4, filtered and the solvent was evaporated. The residue was purified by column chromatography over silica gel (eluent: CH2Cl2 /CH3OH 97/3). The pure fractions were collected and the solvent was evaporated, yielding 3.7 g (66%) of (±)-2-methoxy-α-[3-(trifluoromethyl)phenyl]-6- quinoline methanol (intermediate 28).

Workup

  1. additionAfter complete addition the mixture
  2. stirringthe mixture was stirred at -78° C. for 30 minutes
  3. customquenched with water (50 ml)
  4. extractionextracted with ethylacetate
  5. customThe organic layer was separated
  6. washwashed with brine
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. customthe solvent was evaporated
  10. customThe residue was purified by column chromatography over silica gel (eluent: CH2Cl2 /CH3OH 97/3)
  11. customThe pure fractions were collected
  12. customthe solvent was evaporated

Sources & evidence

ORD record
ord-68c86418cf27496893ae3caa1b9f8bff
Source dataset
uspto-grants-1999_07
Patent number
US05922734

Reaction notes

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