Hydrochloric Acid → 2-(4-Hydroxy-phenyl)-4-methyl-benzofuran-5-ol

HRID 1794550Notes

Reaction equation

C[O:2][C:3]1[CH:4]=[CH:5][C:6]2[O:10][C:9]([C:11]3[CH:16]=[CH:15][C:14]([O:17]C)=[CH:13][CH:12]=3)=[CH:8][C:7]=2[C:19]=1[CH3:20].Cl.N1C=CC=CC=1.Cl>C(OCC)(=O)C>[OH:17][C:14]1[CH:15]=[CH:16][C:11]([C:9]2[O:10][C:6]3[CH:5]=[CH:4][C:3]([OH:2])=[C:19]([CH3:20])[C:7]=3[CH:8]=2)=[CH:12][CH:13]=1

Participants

Conditions

Temperature: 200 °C

Procedure

The crude 5-Methoxy-2-(4-methoxyphenyl)-4-methylbenzofuran 136 (0.134 g) was taken into a sealed tube along with enough pyridine hydrochloride to fill the tube halfway and heated at 200° C. for 2.5 hours. The reaction was dissolved into a mixture of ethyl acetate and 1 N HCl. The layers were separated and the aqueous layer was extracted with ethyl acetate (2×). The combined organics was washed with 1 N HCl (1×), water (1×) and then dried over magnesium sulfate, filtered and concentrated. The resulting material was purified by column chromatography on silica gel, using 30% ethyl acetate in hexanes as the eluent to yield the desired product (0.090 g, 23.4% based on starting 4-Bromo-5-methoxy-2-(4-methoxyphenyl)-benzofuran from two runs) as a tan powder: Mp. 221–222° C.; 1H NMR (DMSO-d6) δ 9.81 (s, 1 H), 8.94 (s, 1 H), ) 7.70 (d, 2 H, J=8.6 Hz), 7.16 (d, 1 H, J=8.9 Hz), 7.14 (s, 1 H), 6.86 (d, 2 H, J=8.6 Hz), 6.72 (d, 1 H, J=8.6 Hz), 2.27 (s, 3 H); MS 241 (M+H)+.

Workup

customThe layers were separated
extractionthe aqueous layer was extracted with ethyl acetate (2×)
washThe combined organics was washed with 1 N HCl (1×), water (1×)
dry with materialdried over magnesium sulfate
filtrationfiltered
concentrationconcentrated
customThe resulting material was purified by column chromatography on silica gel

Sources & evidence

ORD record: ord-66c66fbdb972485e964625d48e8f3ace
Source dataset: uspto-grants-2006_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07022733B2

Reaction notes

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