Sodium hydride → 4-[(6-Methoxy-3-methyl-2-phenyl-1-naphthyl)oxy]benzaldehyde

HRID 1992823Notes

Reaction equation

HRID 1992823 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][CH:25]=1>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][CH:25]=2)[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 680234-FluorobenzaldehydeHCID 685363886-Methoxy-3-methyl-2-phenyl-1-naphthol

Product 1

HCID 860871594-[(6-Methoxy-3-methyl-2-phenyl-1-naphthyl)oxy]benzaldehydeYield 66%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Conditions

Temperature
70 °C

Procedure

A solution of crude 3-methyl-6-(methyloxy)-2-phenyl-1-naphthalenol (7) (1.83 g) in DMF (8 mL) was slowly added dropwise to an ice-water cooled suspension of NaH (60% dispersion in oil) (0.179 g, 4.48 mmol) in DMF (8 mL) with stirring under N2. The ice-water bath was removed and the reaction mixture was allowed to stir at RT for 10 min. To the reaction mixture was added a solution of 4-fluorobenzaldehyde (0.9 mL, 1.04 g, 8.39 mmol) in DMF (3 mL). The reaction mixture was heated at 70° C. for 18 h. The reaction mixture was partially concentrated and the crude product was partitioned between CH2Cl2 and H2O. The organic phase was separated, dried over MgSO4, filtered, and the filtrate was concentrated to give the crude title compound. The crude product was purified by flash chromatography over SiO2 with hexanes:EtOAc (9:1) to give 1.04 g (66%) of compound (8) as a yellow amorphous solid. 1H NMR (400 MHz; DMSO-d6): δ 2.19 (s, 3H), 3.88 (s, 3H), 6.78 (d, J=8.6 Hz, 2H), 7.09 (dd, J=2.6 Hz, 9.1 Hz, 1H), 7.19 (m, 2H), 7.24 (m, 1H), 7.30 (m, 2H), 7.38 (d, J=2.4 Hz, 1H), 7.53 (d, J=7.2 Hz, 1H), 7.70 (d, J=8.7 Hz, 2H), 7.75 (s, 1H), 9.78 (s, 1H). AP LRMS m/z 369 (M+H)+.

Workup

  1. temperaturecooled
  2. customThe ice-water bath was removed
  3. stirringto stir at RT for 10 min
  4. concentrationThe reaction mixture was partially concentrated
  5. customthe crude product was partitioned between CH2Cl2 and H2O
  6. customThe organic phase was separated
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationthe filtrate was concentrated
  10. customto give the crude title compound
  11. customThe crude product was purified by flash chromatography over SiO2 with hexanes:EtOAc (9:1)

Sources & evidence

ORD record
ord-e02131036c0649e78e304db31df3a747
Source dataset
uspto-grants-2010_01
Patent number
US07649093B2

Reaction notes

Loading…