Water → 4-{[3-Ethyl-6-(methyloxy)-2-phenyl-1-naphthalenyl]oxy}benzaldehyde

HRID 1992853Notes

Reaction equation

HRID 1992853 reaction equation
[H-].[Na+].[CH2:3]([C:5]1[C:6]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[C:7]([OH:17])[C:8]2[C:13]([CH:14]=1)=[CH:12][C:11]([O:15][CH3:16])=[CH:10][CH:9]=2)[CH3:4].F[C:25]1[CH:32]=[CH:31][C:28]([CH:29]=[O:30])=[CH:27][CH:26]=1.O>CN(C=O)C>[CH2:3]([C:5]1[C:6]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[C:7]([O:17][C:25]2[CH:32]=[CH:31][C:28]([CH:29]=[O:30])=[CH:27][CH:26]=2)[C:8]2[C:13]([CH:14]=1)=[CH:12][C:11]([O:15][CH3:16])=[CH:10][CH:9]=2)[CH3:4]

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 680234-FluorobenzaldehydeHCID 685377153-Ethyl-6-(methyloxy)-2-phenyl-1-naphthalenol

Product 1

HCID 860871094-{[3-Ethyl-6-(methyloxy)-2-phenyl-1-naphthalenyl]oxy}benzaldehydeYield 86%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

To a suspension of NaH (60% in mineral oil, 78 mg, 1.95 mmol) in DMF (15 mL) at 0° C. was added a solution of 3-ethyl-6-(methyloxy)-2-phenyl-1-naphthalenol (57) (0.52 g, 1.86 mmol) in DMF (5 mL). The mixture was stirred at room temperature for 10 min. 4-Fluorobenzaldehyde (0.47 g, 3.72 mmol) in DMF (3 mL) was added and the resulting mixture was heated at 70° C. for 36 h. Cooled to room temperature, the mixture was poured into water (50 mL) and extracted with EtOAc. The extracts were combined and washed with brine, dried over Na2SO4, filtered, and the filtrate was concentrated to give the crude product as a dark brown oil. The crude product was purified by flash chromatography over SiO2 with hexanes:EtOAc (25:1) to give 0.61 g (86%) of compound 58 as a light yellow foam. 1H NMR (400 MHz, CDCl3): δ 1.13 (t, J=7.5 Hz, 3H), 2.57 (q, J=7.5 Hz, 2H), 3.94 (s, 3H), 6.68 (d, J=8.6 Hz, 2H), 7.06 (dd, J1=9.2 Hz, J2=2.4 Hz, 1H), 7.08-7.15 (m, 2H), 7.17-7.27 (m, 4H), 7.58-7.64 (m, 3H), 7.67 (d, J=9.2 Hz, 1H), 9.79 (s, 1H). LCMS (APCI): m/z 383 (M+H)+.

Workup

  1. temperaturethe resulting mixture was heated at 70° C. for 36 h
  2. temperatureCooled to room temperature
  3. extractionextracted with EtOAc
  4. washwashed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationthe filtrate was concentrated
  8. customto give the crude product as a dark brown oil
  9. customThe crude product was purified by flash chromatography over SiO2 with hexanes:EtOAc (25:1)

Sources & evidence

ORD record
ord-d52d66b8820042ccaf6bf50a0eb91d97
Source dataset
uspto-grants-2010_01
Patent number
US07649093B2

Reaction notes

Loading…