Water → 3-(3,5-Dimethoxyphenyl)-2-[4-(4-formylphenoxy)-phenyl]-propionic acid methyl ester

HRID 2238249Notes

Reaction equation

HRID 2238249 reaction equation
[H-].[Na+].[CH3:3][O:4][C:5](=[O:25])[CH:6]([C:18]1[CH:23]=[CH:22][C:21]([OH:24])=[CH:20][CH:19]=1)[CH2:7][C:8]1[CH:13]=[C:12]([O:14][CH3:15])[CH:11]=[C:10]([O:16][CH3:17])[CH:9]=1.F[C:27]1[CH:34]=[CH:33][C:30]([CH:31]=[O:32])=[CH:29][CH:28]=1.O>CN(C=O)C>[CH3:3][O:4][C:5](=[O:25])[CH:6]([C:18]1[CH:19]=[CH:20][C:21]([O:24][C:27]2[CH:34]=[CH:33][C:30]([CH:31]=[O:32])=[CH:29][CH:28]=2)=[CH:22][CH:23]=1)[CH2:7][C:8]1[CH:9]=[C:10]([O:16][CH3:17])[CH:11]=[C:12]([O:14][CH3:15])[CH:13]=1

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 680234-FluorobenzaldehydeHCID 21051258HCID 21051258, compound

Product 1

HCID 210512573-(3,5-Dimethoxyphenyl)-2-[4-(4-formylphenoxy)-phenyl]-propionic acid methyl esterYield 69.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
80 °C

Procedure

To a suspension of sodium hydride (60% in oil, 0.25 g, 6.3 mmol) in DMF (2 mL) under argon, 15 (2.0 g, 6.3 mmol) in dry DMF (3 mL) was added. To the resulting yellow solution, 4-fluorobenzaldehyde (0.68 mL, 6.3 mmol) was added and heated at 80° C. for 18 h. The reaction mixture was cooled to room temperature, water (20 mL) was added and extracted with ethyl acetate (3×50 mL). The organic layer was dried over anhydrous sodium sulfate, filtered and solvent was evaporated. An ethyl acetate solution of crude product was filtered through a small bed of silica gel to yield 16 (1.83 g, 69%) as oil: 1HNMR (400 MHz, DMSO-d6): δ 9.91 (s, 1H), 7.84 (d, J=8.7 Hz, 2H), 7.33 (d, J=8.7 Hz, 2H), 7.04 (d, J=5.4 Hz, 2H), 7.01 (d, J=5.4 Hz, 2H), 6.30 (t, J=2.1 Hz, 1H), 6.25 (d, J=2.1 Hz, 2H), 3.86 (t, J=7.8 Hz, 1 Hz), 3.76 (s, 6H), 3.66 (s, 3H), 3.36 (dd, J=12.6 and 8.1 Hz, 1H), 2.97 (dd, J=13.5 and 7.5 Hz, 1H); MS (EI) m/z 421 [M]+.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. extractionextracted with ethyl acetate (3×50 mL)
  3. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. customsolvent was evaporated
  6. filtrationAn ethyl acetate solution of crude product was filtered through a small bed of silica gel

Sources & evidence

ORD record
ord-aeb71dff8f0a4dd3a7a6ef7e0c085883
Source dataset
uspto-grants-2010_05
Patent number
US07718682B2

Reaction notes

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