Carbon Dioxide → 3,5,3'-Trihydroxy-biphenyl-4-carboxylic acid methyl ester

HRID 1375682Notes

Reaction equation

HRID 1375682 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([OH:15])[CH:10]=2)[CH:5]=[C:6]([OH:8])[CH:7]=1.[C:16](=[O:18])=[O:17].O[CH2:20]C(CO)O>>[CH3:20][O:17][C:16]([C:7]1[C:2]([OH:1])=[CH:3][C:4]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([OH:15])[CH:10]=2)=[CH:5][C:6]=1[OH:8])=[O:18]

Participants

4

Reactant 3

HCID 280Carbon DioxideHCID 753GlycerolHCID 88736[1,1'-Biphenyl]-3,3',5-triol

Product 1

HCID 695078493,5,3'-Trihydroxy-biphenyl-4-carboxylic acid methyl esterYield 26%

Conditions

Temperature
120 °C

Procedure

To 308 mg (1.52 mmol) of 3,5,3′-trihydroxybiphenyl was added 400 mg (4.0 mmol) of KHCO3, then 1 ml of glycerol. The reaction was stirred at 130° C. under 1 atm of CO2 for 1 hour. Following this period of heating, the thick mixture was transferred to a sealed tube, the space above the mixture was purged with CO2, then the reaction was heated at 120° C. for 15 hour, and at ambient temperature for 96 hours. The reaction was diluted with 10 mL of water, 5 mL of 1M HCl was added slowly, then the mixture was extracted with ethyl acetate (3×5 mL). The combined organic layers were back extracted with water (1×5 mL), and brine (1×5 mL), dried over MgSO4, filtered, and concentrated to a dark residue. This was taken up in ethyl acetate and methanol, and treated with ethereal diazomethane until the acid was no longer visible by TLC and a new, higher Rf spot appeared (40% ethyl acetate:hexanes). The product was purified by silica gel chromatography, eluting with 40% ethyl acetate:hexanes to give 100 mg (26%) of 3,5,3′-trihydroxy-biphenyl-4-carboxylic acid methyl ester as a white solid. 1H NMR (300 MHz, d6-DMSO) δ 10.15 (bs, 2H), 9.56 (bs, 1H), 7.25 (t, 1H, J=7.8 Hz), 6.97 (dd, 1H, J=1.0, 9.2 Hz), 6.92 (t, 1H, J=2.0 Hz), 6.87 (dd, 1H, J=2.4, 8.0 Hz), 6.57 (s, 2H), 3.33 (s, 3H); MS (ESI) m/z=259 (M−H).

Workup

  1. waitFollowing this period
  2. temperatureof heating
  3. customthe thick mixture was transferred to a sealed tube
  4. customthe space above the mixture was purged with CO2
  5. additionThe reaction was diluted with 10 mL of water, 5 mL of 1M HCl
  6. additionwas added slowly
  7. extractionthe mixture was extracted with ethyl acetate (3×5 mL)
  8. extractionThe combined organic layers were back extracted with water (1×5 mL), and brine (1×5 mL)
  9. dry with materialdried over MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated to a dark residue
  12. additionmethanol, and treated with ethereal diazomethane until the acid
  13. customThe product was purified by silica gel chromatography
  14. washeluting with 40% ethyl acetate

Sources & evidence

ORD record
ord-c252a69003c84d7c92b28921dc9bbb5f
Source dataset
uspto-grants-2007_01
Patent number
US07169797B2

Reaction notes

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