Sodium hydride → 4-{[3-Methyl-6-(methyloxy)-2-phenyl-1-naphthalenyl]oxy}-3-(trifluoromethyl)benzaldehyde

HRID 1992837Notes

Reaction equation

HRID 1992837 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[C:9]([OH:13])=[C:8]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[C:7]([CH3:20])=[CH:6]2.[H-].[Na+].F[C:24]1[CH:31]=[CH:30][C:27]([CH:28]=[O:29])=[CH:26][C:25]=1[C:32]([F:35])([F:34])[F:33]>CN(C=O)C>[CH3:20][C:7]1[C:8]([C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)=[C:9]([O:13][C:24]2[CH:31]=[CH:30][C:27]([CH:28]=[O:29])=[CH:26][C:25]=2[C:32]([F:33])([F:35])[F:34])[C:10]2[C:5]([CH:6]=1)=[CH:4][C:3]([O:2][CH3:1])=[CH:12][CH:11]=2

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 5222694-Fluoro-3-(trifluoromethyl)benzaldehydeHCID 685363886-Methoxy-3-methyl-2-phenyl-1-naphthol

Product 1

HCID 866166434-{[3-Methyl-6-(methyloxy)-2-phenyl-1-naphthalenyl]oxy}-3-(trifluoromethyl)benzaldehydeYield 61.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

Compound 7 (215 mg, 0.81 mmol, 1 equiv) was dissolved in DMF (5 mL) and cooled to 0° C. under N2. Sodium hydride, 60% dispersion (36 mg, 0.89 mmol, 1.1 equiv), followed by 4-fluoro-3-(trifluoromethyl)benzaldehyde (311 mg, 1.62 mmol, 2 equiv) were added and the entire reaction mixture was heated to 70° C. for 3 days. The mixture was then partitioned between EtOAc (50 mL) and H2O (50 mL). The organic layer was washed with saturated aqueous NaCl (100 mL), dried over Na2SO4, filtered and concentrated to dryness. The residue was purified by silica gel flash column chromatography (10% EtOAc in hexanes) to provide compound 33 (216 mg, 61%) as a clear oil. 1HNMR (400 MHz, DMSO-d6): δ 9.84 (s, 1H), 8.10 (m, 1H), 7.87 (m, 1H), 7.81 (s, 1H), 7.48-7.13 (m, 8H), 6.64 (m, 1H), 3.88 (s, 3H), 2.22 (s, 3H). MS m/z 437.4 (M+H)+.

Workup

  1. additionwere added
  2. customthe entire reaction mixture
  3. temperaturewas heated to 70° C. for 3 days
  4. customThe mixture was then partitioned between EtOAc (50 mL) and H2O (50 mL)
  5. washThe organic layer was washed with saturated aqueous NaCl (100 mL)
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated to dryness
  9. customThe residue was purified by silica gel flash column chromatography (10% EtOAc in hexanes)

Sources & evidence

ORD record
ord-e75dc74180e04a838ccb2fb499726226
Source dataset
uspto-grants-2010_01
Patent number
US07649093B2

Reaction notes

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