Hydrochloric Acid → Ethyl 4-methoxy-3-methyl-2-benzofurancarboxylate

HRID 1084853Notes

Reaction equation

HRID 1084853 reaction equation
[CH3:1][C:2]1[C:6]2[C:7]([OH:11])=[CH:8][CH:9]=[CH:10][C:5]=2[O:4][C:3]=1[C:12]([O:14][CH2:15][CH3:16])=[O:13].[C:17]([O-])([O-])=O.[K+].[K+].CI.Cl>CC(C)=O.O>[CH3:1][C:2]1[C:6]2[C:7]([O:11][CH3:17])=[CH:8][CH:9]=[CH:10][C:5]=2[O:4][C:3]=1[C:12]([O:14][CH2:15][CH3:16])=[O:13]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 748649Ethyl 4-hydroxy-3-methyl-1-benzofuran-2-carboxylate

Product 1

HCID 9497663Ethyl 4-methoxy-3-methyl-2-benzofurancarboxylate

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 962WaterSolvent

Procedure

To a solution of ethyl 3-methyl-4-hydroxybenzofuran-2-carboxylate 20 (5.02 g, 22.8 mmol) in acetone (85 mL) was added sequentially K2CO3 (6.3 g, 45.6 mmol) and methyl iodide (6.47 g, 45.6 mmol). The resulting suspension was heated to reflux with stirring for 15 hours, allowed to cool, diluted with water (125 mL), and acidified with 2N HCl (50 mL). The resulting mixture was extracted with ethyl acetate (1×100 mL then 2×50 mL) and the combined extracts were dried and concentrated to a brown oil. Chromatographic purification (Preparative HPLC, 5% ethyl acetate in hexane as eluant) afforded pure ethyl 3-methyl-4-methoxybenzofuran-2-carboxylate as a colorless oil which crystallized on standing. mp 67°-69° C.; 1H NMR d 1.47 (3H, t, J=6 Hz), 2.78 (3H, s), 3.96 (3H, s), 4.48 (2H, q, J=6 Hz), 6.66 (1H, d, J=8 Hz), 7.16 (1H, d, J=8 Hz), 7.36 (1H, t, J=8 Hz).

Workup

  1. temperatureThe resulting suspension was heated
  2. temperatureto reflux
  3. temperatureto cool
  4. extractionThe resulting mixture was extracted with ethyl acetate (1×100 mL
  5. custom2×50 mL) and the combined extracts were dried
  6. concentrationconcentrated to a brown oil
  7. customChromatographic purification (Preparative HPLC, 5% ethyl acetate in hexane as eluant)

Sources & evidence

ORD record
ord-e83c16cf1ca94e40a4f6a96a73a81679
Source dataset
uspto-grants-1991_04
Patent number
US05006549

Reaction notes

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