Guaiacol → HCID 66906135, compound

HRID 1915129Notes

Reaction equation

HRID 1915129 reaction equation
[C:1]1([O:8][CH3:9])[C:2](=[CH:4][CH:5]=[CH:6][CH:7]=1)[OH:3].[H-].[Na+].[CH3:12][O:13][C:14](=[O:26])[C:15]1[C:16](=[C:21](I)[CH:22]=[CH:23][CH:24]=1)[C:17]([O:19][CH3:20])=[O:18]>N1C=CC=CC=1.[Cu]Br>[CH3:12][O:13][C:14](=[O:26])[C:15]1[C:16](=[C:21]([O:3][C:2]2[CH:4]=[CH:5][CH:6]=[CH:7][C:1]=2[O:8][CH3:9])[CH:22]=[CH:23][CH:24]=1)[C:17]([O:19][CH3:20])=[O:18]

Participants

6

Reactant 3

HCID 460GuaiacolHCID 24758Sodium hydrideHCID 2326127Dimethyl 3-iodophthalate

Product 1

HCID 66906135HCID 66906135, compoundYield 38.2%

Reagents, catalysts & solvents 2

HCID 24593copper(I) bromideCatalystHCID 1049PyridineSolvent

Procedure

A mixture of guaiacol (0.77 g, 6.2 mmol), copper (I) bromide (0.89 g, 6.2 mmol), and sodium hydride (0.3 g of a 60% dispersion, 7.5 mmol) in 100 mL pyridine was heated to reflux and stirred under nitrogen for 15 min. 3-Iodophthalic acid dimethyl ester (2.0 g, 6.2 mmol) was added, and the resulting mixture was stirred at reflux for 20 h. The mixture was cooled to room temperature and quenched by the addition of saturated NH4Cl (15 mL). Volatiles were removed under reduced pressure. The residue was partitioned between dilute aqueous HCl (100 mL) and ethyl acetate (100 mL), and the aqueous phase was extracted with ethyl acetate (100 mL). The combined organic extracts were washed with dilute aqueous HCl (2×100 mL), saturated Na2CO3 (2×100 mL), again with dilute aqueous HCl (2×100 mL) and finally with water (100 mL), and were evaporated. Chromatography in hexanes-ethyl acetate gradient provided 0.75 g of 3-(2-methoxy-phenoxy)-phthalic acid dimethyl ester, eluting at 25-30% ethyl acetate, in 38% yield; 1H NMR (CDCl3) δ 3.79 (s, 3H), 3.91 (s, 3H), 3.95 (s, 3H), 6.86-6.91 (m, 1H), 6.93-7.01 (m, 2H), 7.05 (dd, J=7.9 Hz. J=1.6 Hz, 1H), 7.13-7.20 (m, 1H), 7.30 (t, J=8.0 Hz, 1H), 7.66-7.69 (m, 1H).

Workup

  1. temperaturewas heated
  2. temperatureto reflux
  3. stirringthe resulting mixture was stirred
  4. temperatureat reflux for 20 h
  5. customquenched by the addition of saturated NH4Cl (15 mL)
  6. customVolatiles were removed under reduced pressure
  7. customThe residue was partitioned between dilute aqueous HCl (100 mL) and ethyl acetate (100 mL)
  8. extractionthe aqueous phase was extracted with ethyl acetate (100 mL)
  9. washThe combined organic extracts were washed with dilute aqueous HCl (2×100 mL), saturated Na2CO3 (2×100 mL), again with dilute aqueous HCl (2×100 mL) and finally with water (100 mL)
  10. customwere evaporated

Sources & evidence

ORD record
ord-040c95ae0a39448d82b19d0bd19983e8
Source dataset
uspto-grants-2013_12
Patent number
US08614328B2

Reaction notes

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