Acetic Anhydride → 6-Benzofurancarboxylic acid, 4-(acetyloxy)-2-methyl-, ethyl ester
Reaction equation
[CH2:1]([O:3][C:4](/[C:6](=[CH:11]/[C:12]1[O:13][C:14]([CH3:17])=[CH:15][CH:16]=1)/[CH2:7][C:8]([OH:10])=O)=[O:5])[CH3:2].[C:18](OC(=O)C)(=[O:20])[CH3:19].C([O-])(=O)C.[Na+]>>[C:18]([O:10][C:8]1[C:16]2[CH:15]=[C:14]([CH3:17])[O:13][C:12]=2[CH:11]=[C:6]([C:4]([O:3][CH2:1][CH3:2])=[O:5])[CH:7]=1)(=[O:20])[CH3:19]Participants
Procedure
To a vigorously stirred solution of (E)-3-(ethoxycarbonyl)-4-(5-methylfuran-2-yl)but-3-enoic acid (I-1a: 326.6 g, 1.371 mol) in acetic anhydride (1.77 L, 18.72 mol) at room temperature was added sodium acetate (193 g, 2350 mmol) in one portion. The reaction mixture was then heated at reflux for 2.5 hours. After cooling to room temperature, the mixture was concentrated in vacuo (all batches were combined at this point). The resulting residue was suspended in dichloromethane (1.5 L) and filtered, washing the solids with dichloromethane (3×500 mL). The combined filtrate and washings were then washed with sodium hydrogencarbonate (2×1 L of a saturated aqueous solution) and brine (2 L), then concentrated in vacuo to give desired ethyl 4-acetoxy-2-methylbenzofuran-6-carboxylate (I-1b: 549.03 g, quantitative). 1H NMR (CDCl3, 300 MHz) δ ppm 8.00-7.99 (m, 1H), 7.64 (d, 1H), 6.32-6.32 (m, 1H), 4.38 (q, 2H), 2.47 (d, 3H), 2.37 (s, 3H), 1.39 (t, 3H).
Workup
- temperatureThe reaction mixture was then heated
- temperatureat reflux for 2.5 hours
- concentrationthe mixture was concentrated in vacuo (all batches
- filtrationfiltered
- washwashing the solids with dichloromethane (3×500 mL)
- washThe combined filtrate and washings were then washed with sodium hydrogencarbonate (2×1 L of a saturated aqueous solution) and brine (2 L)
- concentrationconcentrated in vacuo
Sources & evidence
- ORD record
- ord-fd82e14a1e9349a8bd3730f3cdf32650
- Source dataset
- uspto-grants-2014_05
- Patent number
- US08735396B2
Reaction notes
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