4-Benzofurancarboxylic acid, methyl ester

A mixture of 130 (3.88 g, 14.6 mmol), DPPP (0.180 g, 0.44 mmol), triethylamine (4.07 mL, 29.2 mmol) and Pd(OAc)A mixture of the above sulfonate (3.88 g, 14.6 mmol), DPPP(0.180 g, 0.44 mmol), triethylamine (4.07 mL, 29.2 mmol) and Pd(OAc)2 (0.098 g, 0.44 mmol) in DMSO (50 mL) and MeOH (50 mL)in a Berghof pressure reactor was evacuated then purged threetimes with carbon monoxide. The mixture was heated to 80 Cfor 18 h under 60 psi of carbon monoxide pressure, cooled and partitioned between EtOAc and water. Column chromatographywith 3:1 hexanes:DCM eluted traces of impurities while elutionwith DCM gave methyl benzofuran-4-carboxylate (2.08 g, 81percent).1H NMR (CDCl3) d 7.99 (dd, J = 7.7, 0.9 Hz, 1H), 7.74 (d, J = 2.2 Hz, 1H), 7.70 (dt, J = 8.2, 0.9 Hz, 1H), 7.33–7.39 (m, 2H), 3.99 (s, 3H).Example 5Aromatization Unless mentioned otherwise, all the volumes are calculated from 2-methoxy-2, 3-dihydrobenzofuran-4-carboxylic acid methyl ester (II).841 g of methane sulfonic acid (8.75 mol, 2 mol/mol) are added to the previous toluene solution while maintaining the temperature at 20° C.The reaction medium is stirred at 20° C. for 2 hours. The reaction medium is then cooled to 10° C., 3 water volumes are added while maintaining the temperature of the medium at 10° C.The phases are separated and the lower aqueous phase is then extracted with 2 volumes of toluene. The collected toluene phases are washed with 2.x.2 volumes of water and then with 2.x.2 volumes of 1N soda.The insolubles formed in the basic medium are left in the organic phase, the toluene phase is clarified and introduced as such to the following step. 747 g of 4-benzofuran-carboxylic acid methyl ester are obtained in solution in toluene with a 98percent yield.The reaction medium is extracted and then concentrated.A white solid is obtained corresponding to the compound of formula (I), 4-benzofuran-carboxylic acid methyl ester.The product from Step A (8.0 g, 41.0 mmol) was stirred in HA mixture of 130 (3.88 g, 14.6 mmol), DPPP (0.180 g, 0.44 mmol), triethylamine (4.07 mL, 29.2 mmol) and Pd(OAc)2 (0.098 g, 0.44 mmol) in DMSO (50 mL) and MeOH (50 mL) in a Berghof pressure reactor was evacuated then purged three times with carbon monoxide. The mixture was heated to 80 C for 18 h under 60 psi of carbon monoxide pressure, cooled and partitioned between EtOAc and water. Column chromatography with 3 : 1 hexanes:DCM eluted traces of impurities while elution with DCM gave 131 (2.08 g, 81%). 1H NMR (CDC13) delta 7.99 (dd, J = 7.7, 0.9 Hz, 1H), 7.74 (d, J = 2.2 Hz, 1H), 7.70 (dt, J = 8.2, 0.9 Hz, 1H), 7.33-7.39 (m, 2H), 3.99 (s, 3H).A mixture of the above sulfonate (3.88 g, 14.6 mmol), DPPP(0.180 g, 0.44 mmol), triethylamine (4.07 mL, 29.2 mmol) and Pd(OAc)2 (0.098 g, 0.44 mmol) in DMSO (50 mL) and MeOH (50 mL)in a Berghof pressure reactor was evacuated then purged threetimes with carbon monoxide. The mixture was heated to 80 Cfor 18 h under 60 psi of carbon monoxide pressure, cooled and partitioned between EtOAc and water. Column chromatographywith 3:1 hexanes:DCM eluted traces of impurities while elutionwith DCM gave The product from Step A (8.0 g, 41.0 mmol) was stirred in H3PO4 (85%, 50 ml) at room temperature for 30 minutes. The resulting cloudy mixture was diluted with water and extracted (4*) with diethyl ether. The combined organic extracts were washed with brine, dried over anhydrous sodium sulfate, filtered, and the solvent removed in vacuo. The crude material was purified by flash chromatography on silica gel (20:1 hexanes/ethyl acetate) to afford benzofuran methyl ester 3.87 g (53%) as a light yellow oil: 1H NMR (300 MHz, CDCl3) delta7.99 (d, 1H, J=7.1 Hz), 7.68-7.74 (m, 2H), 7.32-7.38 (m, 2H), 3.99 (m, 3H); CI MS m/z=177 [C10H8O3+H]+.

Molecular Weight:176.17
XLogP3:2.2
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:2
Exact Mass:176.047344113
Monoisotopic Mass:176.047344113
Topological Polar Surface Area:39.4
Heavy Atom Count:13
Complexity:202
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes