Hydroxyphenylacetic acid → HCID 58748966, compound

HRID 505487Notes

Reaction equation

HRID 505487 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([OH:11])=[O:10])=[CH:4][CH:3]=1.C([O-])([O-])=O.[K+].[K+].F[C:19]1[CH:26]=[CH:25][C:22]([CH:23]=[O:24])=[CH:21][CH:20]=1.O>CN(C=O)C>[CH:23]([C:22]1[CH:25]=[CH:26][C:19]([O:1][C:2]2[CH:3]=[CH:4][C:5]([CH2:8][C:9]([OH:11])=[O:10])=[CH:6][CH:7]=2)=[CH:20][CH:21]=1)=[O:24]

Participants

6

Reactant 4

HCID 127Hydroxyphenylacetic acidHCID 962WaterHCID 11430Potassium CarbonateHCID 680234-Fluorobenzaldehyde2×

Product 1

HCID 58748966HCID 58748966, compoundYield 25.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
78 °C

Procedure

To a suspension of 4-hydroxyphenylacetic acid (5.8 g, 38.2 mmoles) in dry DMF (50 mL) under argon, was added K2CO3 (15.8 g, 114.5 mmoles), and 4-fluorobenzaldehyde (23.7 g, 190.8 mmoles), and the reaction mixture was stirred at 78±2° C. for 18 hours under argon (Note: the reaction mixture becomes very viscous soon after the addition of 4-fluorobenzaldehyde, which slowly liquefies again). Subsequently the reaction mixture was cooled to room temperature, then poured into water (250 mL) and stirred for 15 minutes. The aqueous layer was extracted with ethyl acetate (2×75 mL); the organic layer was discarded and the resulting aqueous layer was acidified with HCl (˜6M) to pH 2.0. The aqueous layer was extracted with ethyl acetate (2×100 mL), the combined organic layers were washed with brine (50 mL), dried over anhydrous magnesium sulfate and evaporated under reduced pressure to afford a mixture which was purified by silica gel chromatography using hexane-ethyl acetate (7:3) containing 1% acetic acid as eluent to yield a pale yellow solid (2.5 g, 25.6%). 1H NMR (400 MHz, DMSO-d6): δ ppm: 12.34 (br, 1H), 9.92 (s, 1H), 7.92 (d, J=8.8 Hz, 2H), 7.35 (d, J=8.8 Hz, 2H), 7.11 (overlapped d, J=8.8 Hz, 2H), 7.10 (overlapped d, J=8.8 Hz, 2H), 3.61 (s, 2H).

Workup

  1. temperatureSubsequently the reaction mixture was cooled to room temperature
  2. stirringstirred for 15 minutes
  3. extractionThe aqueous layer was extracted with ethyl acetate (2×75 mL)
  4. extractionThe aqueous layer was extracted with ethyl acetate (2×100 mL)
  5. washthe combined organic layers were washed with brine (50 mL)
  6. dry with materialdried over anhydrous magnesium sulfate
  7. customevaporated under reduced pressure
  8. customto afford a mixture which
  9. customwas purified by silica gel chromatography
  10. additioncontaining 1% acetic acid as eluent

Sources & evidence

ORD record
ord-3733df224f654be1946ef0a0964e8b9a
Source dataset
uspto-grants-2010_08
Patent number
US07781464B2

Reaction notes

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