Cesium carbonate → 6-[2-(Difluoromethoxy)-4-(trifluoromethyl)phenoxy]-1-benzofuran

HRID 2118098Notes

Reaction equation

[O:1]1[C:5]2[CH:6]=[C:7]([OH:10])[CH:8]=[CH:9][C:4]=2[CH:3]=[CH:2]1.[F:11][CH:12]([F:25])[O:13][C:14]1[CH:19]=[C:18]([C:20]([F:23])([F:22])[F:21])[CH:17]=[CH:16][C:15]=1F.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.C(OCC)(=O)C>[F:25][CH:12]([F:11])[O:13][C:14]1[CH:19]=[C:18]([C:20]([F:21])([F:22])[F:23])[CH:17]=[CH:16][C:15]=1[O:10][C:7]1[CH:8]=[CH:9][C:4]2[CH:3]=[CH:2][O:1][C:5]=2[CH:6]=1

Participants

Conditions

Temperature: 110 °C

Procedure

To a stirred solution of 1-benzofuran-6-ol (13.4 g, 100 mmol) and 2-(difluoromethoxy)-1-fluoro-4-trifluoromethylbenzene (29.9 g, 130 mmol) in DMF (300 mL) was added cesium carbonate (65.2 g, 200 mmol). The reaction mixture was stirred at 75° C. for 16 hours (or at 110° C. for 2 hours). After cooling to room temperature, it was diluted with ethyl acetate, washed with water (2×) and brine, dried over magnesium sulfate, filtered and concentrated. The crude product was purified on a silica gel column, eluting with ethyl acetate (0-20%) in hexanes. The final product was collected as a colorless oil. 1H NMR (CDCl3, δ ppm): 6.7 (t, 1H, J=74 Hz), 6.8 (s, 1H), 7.0 (m, 2H), 7.2 (s, 1H), 7.4 (d, 1H), 7.6 (m, 3H).

Workup

temperatureAfter cooling to room temperature
washwashed with water (2×) and brine
dry with materialdried over magnesium sulfate
filtrationfiltered
concentrationconcentrated
customThe crude product was purified on a silica gel column
washeluting with ethyl acetate (0-20%) in hexanes
customThe final product was collected as a colorless oil

Sources & evidence

ORD record: ord-2772a64115e54717af41e7972f41ed1c
Source dataset: uspto-grants-2008_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07442808B2

Reaction notes

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