Water → Ethyl 4-[4-(difluoromethyl)phenoxy]-2-methyl-1-benzofuran-6-carboxylate

HRID 1177290Notes

Reaction equation

[OH:1][C:2]1[C:7]2[CH:8]=[C:9]([CH3:11])[O:10][C:6]=2[CH:5]=[C:4]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH:3]=1.Br[C:18]1[CH:23]=[CH:22][C:21]([CH:24]([F:26])[F:25])=[CH:20][CH:19]=1.C([O-])([O-])=O.[Cs+].[Cs+].O>CN(C=O)C.[Cu]I>[F:25][CH:24]([F:26])[C:21]1[CH:22]=[CH:23][C:18]([O:1][C:2]2[C:7]3[CH:8]=[C:9]([CH3:11])[O:10][C:6]=3[CH:5]=[C:4]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH:3]=2)=[CH:19][CH:20]=1

Participants

Conditions

Temperature: 160 °C

Procedure

A mixture of ethyl 4-hydroxy-2-methyl-1-benzofuran-6-carboxylate (252c) (1.10 g, 5 mmol), 1-bromo-4-(difluoromethyl)benzene (1.24 g, 6 mmol), Cs2CO3 (2.44 g, 7.5 mmol) and CuI (5 mg, 0.03 mmol) in DMF (5 mL) was heated in a microwave at 160° C. for 60 minutes. Water was then added and the product was extracted with CHCl3 (3×), dried over MgSO4 and concentrated to give an oil residue. The oil was purified via silica gel chromatography using hexanes/EtOAc (100/0 to 70/30) to give the title compound (710 mg, 41%) as a yellow solid. 1H NMR (300 MHz, CHLOROFORM-D) δ ppm 1.38 (t, J=7.06 Hz, 3 H) 2.44 (s, 3 H) 4.37 (q, J=7.06 Hz, 2 H) 6.22 (d, J=0.94 Hz, 1 H) 6.63 (t, J=56.61 Hz, 1 H) 7.03 (d, J=8.29 Hz, 2 H) 7.46 (d, J=8.29 Hz, 2 H) 7.55 (d, J=1.13 Hz, 1 H) 7.89-8.05 (m, 1 H).

Workup

extractionthe product was extracted with CHCl3 (3×)
dry with materialdried over MgSO4
concentrationconcentrated
customto give an oil residue
customThe oil was purified via silica gel chromatography

Sources & evidence

ORD record: ord-e94ec0f99f3948ad98a3d018b5e49e89
Source dataset: uspto-grants-2010_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07842713B2

Reaction notes

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