Hydroxyphenylacetic acid → 3-(3,5-Dimethoxyphenyl)-2-(4-hydroxyphenyl)-acrylic acid

HRID 2253267Notes

Reaction equation

HRID 2253267 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:8]=[C:9]([O:11][CH3:12])[CH:10]=1)[CH:6]=O.[OH:13][C:14]1[CH:19]=[CH:18][C:17]([CH2:20][C:21]([OH:23])=[O:22])=[CH:16][CH:15]=1.C(OC(=O)C)(=O)C.C(N(CC)CC)C.Cl>[OH-].[Na+]>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:6]=[C:20]([C:17]2[CH:18]=[CH:19][C:14]([OH:13])=[CH:15][CH:16]=2)[C:21]([OH:23])=[O:22])[CH:8]=[C:9]([O:11][CH3:12])[CH:10]=1

Participants

7

Reactant 5

HCID 127Hydroxyphenylacetic acidHCID 313Hydrochloric Acid2×HCID 7918Acetic AnhydrideHCID 8471TriethylamineHCID 817473,5-Dimethoxybenzaldehyde

Product 1

HCID 3567513-(3,5-Dimethoxyphenyl)-2-(4-hydroxyphenyl)-acrylic acidYield 138.7%

Reagents, catalysts & solvents 1

HCID 14798Sodium HydroxideSolvent

Conditions

Temperature
130 °C

Procedure

To a mixture of 3,5-dimethoxybenzaldehyde (120 g, 0.72 mol) and p-hydroxyphenyl acetic acid (110 g, 0.72 mol) was added acetic anhydride (240 mL) and triethylamine (161 mL, 1.6 equiv.). This non-homogeneous mixture on heating becomes homogeneous at ˜70° C. After being stirred at 130° C. for 4 hr, the mixture was cooled to room temperature. HCl (15%, 500 mL) was added to the reaction mixture slowly in 30 min keeping temperature below 5-10° C. The solid was dissolved in 3N aqueous NaOH (1.2 L) and stirred for 0.5 hr. The filtrate was acidified, maintaining a temperature at 25-30° C., with conc. HCl (˜700 mL) to pH 1. The precipitated product was filtered and washed with water to give crude product (˜300 g, wet cake). The crude product was dissolved by heating in ethanol and recrystallized by adding equal volume of water. The product was dried overnight in a vacuum oven at 40° C. Yield: 161 g, 74%. Analysis: 1HNMR (DMSO-d6): δ 12.48 (br, 1H), 9.42 (s, 1H), 7.59 (s, 1H), 6.95 (d, J=8.0 Hz, 2H), 6.76 (d, J=8.0 Hz, 2H), 6.35 (t, J=2.2 Hz, 1H), 6.27 (d, J=2.2 Hz, 2H), 3.56 (s, 6H).

Workup

  1. temperatureThis non-homogeneous mixture on heating
  2. custombecomes homogeneous at ˜70° C
  3. temperaturethe mixture was cooled to room temperature
  4. customtemperature below 5-10° C
  5. stirringstirred for 0.5 hr
  6. temperaturemaintaining a temperature at 25-30° C.
  7. filtrationThe precipitated product was filtered
  8. washwashed with water

Sources & evidence

ORD record
ord-de9330f125d04a8bb2c811b95c1303c0
Source dataset
uspto-grants-2008_01
Patent number
US07323496B2

Reaction notes

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