Potassium Carbonate → 4,5-Dichloro-2-(4-fluoro-2-methoxy-phenoxy)benzaldehyde

HRID 515087Notes

Reaction equation

HRID 515087 reaction equation
[Cl:1][C:2]1[C:9]([Cl:10])=[CH:8][C:5]([CH:6]=[O:7])=[C:4](F)[CH:3]=1.[F:12][C:13]1[CH:18]=[CH:17][C:16]([OH:19])=[C:15]([O:20][CH3:21])[CH:14]=1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.O>[Cl:1][C:2]1[C:9]([Cl:10])=[CH:8][C:5]([CH:6]=[O:7])=[C:4]([O:19][C:16]2[CH:17]=[CH:18][C:13]([F:12])=[CH:14][C:15]=2[O:20][CH3:21])[CH:3]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 27373684-Fluoro-2-methoxyphenolHCID 873173724,5-Dichloro-2-fluorobenzaldehyde

Product 1

HCID 903146634,5-Dichloro-2-(4-fluoro-2-methoxy-phenoxy)benzaldehydeYield 51%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

Crude 4,5-dichloro-2-fluoro-benzaldehyde, 4-fluoro-2-methoxy-phenol (2.31 mL, 20.23 mmol) and K2CO3 (5.59 g, 40.46 mmol) were combined in DMF (100 mL) and heated for ˜30 min at 70° C., then at 55° C. overnight. The reaction was cooled, diluted with water (500 mL) and extracted with diethyl ether. The ether layer was dried over Na2SO4, filtered, and concentrated. Silica gel chromatography using a gradient of ethyl acetate/hexane (0-40%) provided 4,5-dichloro-2-(4-fluoro-2-methoxy-phenoxy)benzaldehyde (3.30 g, 51%) as a crystalline white solid. 1H NMR (400 MHz, DMSO-d6) δ 10.39 (s, 1H), 7.93 (s, 1H), 7.35 (dd, J=8.8, 5.8 Hz, 1H), 7.19 (dd, J=10.7, 2.9 Hz, 1H), 6.92-6.85 (m, 2H), 3.78 (s, 3H) ppm.

Workup

  1. customat 55° C.
  2. customovernight
  3. temperatureThe reaction was cooled
  4. extractionextracted with diethyl ether
  5. dry with materialThe ether layer was dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-6b26299fe04948ffb0f6ad92666ddb5c
Source dataset
uspto-grants-2015_08
Patent number
US09108903B2

Reaction notes

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