2-BENZOFURANACETIC ACID

Compound 5 (117 g) was added dropwise to a stirring suspension of sodium cyanide (37.64 g) in dimethyl sulfoxide (100 ml). The reactor was placed from time to time into an ice bath in order to keep the reaction temperature between 20 C. and 45 C. Addition lasted 60 minutes. The reaction mixture was stirred for another 16 hours, then poured into methylene chloride (500 ml), washed with water (500 ml, then 2*250 ml), and evaporated to dryness. A small sample was purified on a silica gel column, eluding with dichloromethane/hexanes (50:50 v/v). 2-Benzofuraneacetic acid:EXAMPLE 20 Benzofuran-2-yl-acetic acid A solution of compound 8 (5.32 g, 28 mmol) and lithium hydroxide monohydrate (1.24 g, 30 mmol) in tetrahydrofuran (45 mL), water (30 mL), and methanol (12 mL) was stirred for 5 hours at room temperature. Water (60 mL) was added, and the reaction mixture was acidified to pH 4 using 2 M HCl and extracted with dichloromethane (5*150 mL). The organics were dried (MgSO4) and the solvent removed in vacuo. Column chromatography (ethyl acetate:heptane 4:1'ethyl acetate:methanol) gave a brown solid. This was dissolved in ethyl acetate, heptane was added, and the mixture was stirred overnight. Solvent was removed by syringe to give product as a pale brown solid, 17 mmol, 61%. 1 H NMR (400 MHz, CDCl3): delta7.54-7.52 (1H, m); 7.46-7.44 (1H, m); 7.28-7.19 (2H, m); 6.66 (1H, s); 3.88 (2H, s).40 ml of 10% aqueous sodium hydroxide solution was added to the 7.91 g (50.3 mmol) of the acetonitrile derivative and stirring carried out for 4 hours at 100 C. The reaction liquid was cooled and then extracted with dichloromethane. The aqueous layer was acidified with concentrated hydrochloric acid and extracted with dichloromethane, after which drying, filtering and concentration were conducted, and 7.81 g (mmol) of 2-benzofuranacetic acid was obtained.Synthesis of (benzofuran-2-yl)acetic acid The alcohol compound (0.44 g) was dissolved in acetonitrile (8 mL), and triphenylphosphine (0.94 g) and carbon tetrabromide (1.19 g) were added thereto, followed by stirring for two hours at room temperature. The solvent was removed under reduced pressure, and ether (50 mL) was added to the residue, whereby the soluble matter contained in the residue was dissolved. The supernatant was separated through decantation, and the soluble matter contained in the residue was further extracted twice with ether (30 mL). The organic layers were combined and dried over magnesium sulfate, and the solvent was removed under reduced pressure. The residue was purified through silica gel column chromatography (silica gel (15 g), eluent; hexane: ethyl acetate = 20:1), to thereby yield a bromine compound (0.64 g). The compound was dissolved in DMSO (7 mL), and sodium cyanide (0.39 g) was added thereto, followed by stirring for one hour at room temperature. The reaction mixture was added to water, followed by extraction with ether (150 mL). The extract was washed with water and saturated brine and dried over magnesium sulfate, and the solvent was removed under reduced pressure. The residue was purified through silica gel column chromatography (silica gel (12 g), eluent; hexane: ethyl acetate = 7:1), to thereby yield 0.20 g of a nitrile compound (yield 42.0%). The nitrile compound (0.20 g) was dissolved in ethanol (2 mL), and 5N sodium hydroxide (2 mL) was added thereto, followed by refluxing for 5.5 hours. After cooling of the reaction mixture, water was added thereto, and the resultant mixture was washed with ether. The water layer was acidified with concentrated hydrochloric acid, followed by extraction with chloroform (50 mL and 10 mL). The organic layers were combined, washed with saturated brine, and dried over magnesium sulfate, and the solvent was removed under reduced pressure, to thereby yield 0.20 g of the target carboxylic acid (yield 89.2%). NMR delta ppm(CDCl3): 2.04(b, 1H), 3.89(s, 2H), 6.67(s, 1H), 7.16-7.32(m, 2H), 7.45(d, 1H, J=8.1Hz 7.53(d, 1H, J=8.1Hz)

Molecular Weight:176.17
XLogP3:1.8
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:2
Exact Mass:176.047344113
Monoisotopic Mass:176.047344113
Topological Polar Surface Area:50.4
Heavy Atom Count:13
Complexity:202
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes