Hydroxyphenylacetic acid → 4-[7-(acetyloxy)-2-oxo-2H-chromen-3-yl]phenyl acetate

HRID 2171748Notes

Reaction equation

HRID 2171748 reaction equation
[CH:1]1[C:6]([C@H:7]2[CH2:16][O:15][C:14]3[CH:13]=[C:12]([OH:17])[CH:11]=[CH:10][C:9]=3[CH2:8]2)=[CH:5][CH:4]=[C:3]([OH:18])[CH:2]=1.[OH:19][C:20]1C=CC(CC(O)=O)=C[CH:21]=1.[OH:30][C:31]1C=C(O)C=C[C:32]=1C=O.C(OC(=O)C)(=[O:42])C.C(N(C(C)C)CC)(C)C.CN(C)C.C(N(C(C)C)C(C)C)(C)C.CN1CCCCC1.C(=O)(O)[O-].[Na+].C(=O)(O)[O-].[K+].C(=O)([O-])[O-].[K+].[K+].C(=O)([O-])[O-].[Na+].[Na+]>O.C(N(CC)CC)C>[C:20]([O:18][C:3]1[CH:4]=[CH:5][C:6]([C:7]2[C:16](=[O:42])[O:15][C:14]3[C:9]([CH:8]=2)=[CH:10][CH:11]=[C:12]([O:17][C:31](=[O:30])[CH3:32])[CH:13]=3)=[CH:1][CH:2]=1)(=[O:19])[CH3:21]

Participants

15

Reactant 12

HCID 127Hydroxyphenylacetic acidHCID 1146TrimethylamineHCID 72132,4-DihydroxybenzaldehydeHCID 7918Acetic AnhydrideHCID 10340Sodium CarbonateHCID 11430Potassium CarbonateHCID 12291N-MethylpiperidineHCID 61924TriisopropylamineHCID 81531Diisopropylethylamine2×HCID 91469EquolHCID 516892Sodium BicarbonateHCID 516893Potassium Bicarbonate

Product 1

HCID 3840254-[7-(acetyloxy)-2-oxo-2H-chromen-3-yl]phenyl acetate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8471TriethylamineSolvent

Procedure

The first step of the process for preparation of (S)-equol (1) involves Perkin reaction between 4-hydroxy phenyl acetic acid and 2,4-dihydroxy benzaldehyde in presence of an acid anhydride and a base. The most suitable acid anhydride is acetic anhydride although other acid anhydrides may also be used for the reaction. The base may be selected from a group of organic amines like triethylamine, diisopropylethylamine, trimethylamine, triisopropylamine, N-methylpiperidine and inorganic bases like sodium bicarbonate, potassium bicarbonate, potassium biphosphate, sodium biphosphate, potassium carbonate, sodium carbonate. Specifically, the base may be selected from a group of organic amines and more specifically the base may be diisopropylethylamine. The reaction is carried out at a temperature of about 100° C. to about 200° C. for a period of about 30 hours to about 60 hours. Specifically, the reaction is carried out at a temperature of about 90° C. to about 150° C. for a period of about 35 hours to about 45 hours and more specifically the reaction is carried out at a temperature of about 115° C. to about 120° C. for a period of about 38 hours to about 42 hours. After the reaction is completed, the reaction mixture is cooled from about 10° C. to about 30° C. and specifically from about 20° C. to about 25° C. and water is added. The precipitated solid is filtered and washed with water and optionally dried to provide 4-(7-acetoxy-2-oxo-2H-chromen-3-yl)phenyl acetate of formula (3).

Workup

  1. custommay also be used for the reaction
  2. waitThe reaction is carried out at a temperature of about 100° C. to about 200° C. for a period of about 30 hours to about 60 hours
  3. waitSpecifically, the reaction is carried out at a temperature of about 90° C. to about 150° C. for a period of about 35 hours to about 45 hours
  4. waitmore specifically the reaction is carried out at a temperature of about 115° C. to about 120° C. for a period of about 38 hours to about 42 hours
  5. temperaturethe reaction mixture is cooled from about 10° C. to about 30° C. and specifically from about 20° C. to about 25° C.
  6. filtrationThe precipitated solid is filtered
  7. washwashed with water
  8. customoptionally dried

Sources & evidence

ORD record
ord-50650788c9454100852c019b22cb3286
Source dataset
uspto-grants-2015_06
Patent number
US09051291B2

Reaction notes

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