4-BROMO-BENZO[B]THIOPHENE-2-CARBOXYLICACID

Step 3: (0367) A 500 mL single-neck flask was charged with compound 14-c (20 g, 70.4 mmol), tetrahydrofuran (120 ml) and water (100 ml). 4N aqueous sodium hydroxide solution (40 ml) was added under stirring followed by stirring at 70° C. for 1 hour. The reaction mixture was extracted with ethyl acetate (70 ml×2), the pH of the aqueous phase was adjusted with concentrated hydrochloric acid to 12, the precipitated solid was filtered and dried to give compound 14-d (16 g, yield: 88percent).Step 2 4-bromo-benzorb1thiophene-2-carboxylic acidPotassium hydroxide (415.1 g, 7.40 mol) is added to a stirred solution of 2-bromo-6- fluorobenzaldehyde (1.00 Kg, 4.93 mol) and mercaptoacetic acid (453.8 g, 4.93 mol) in dimethylformamide (5.0 L). The resultant solution is brought to and maintained at reflux (136 'C) for 90 min. The reaction mixture is allowed to cool to room temperature and is quenched by the slow addition of hydrochloric acid (2.25 M, 5.90 L) over 5min. The mixture is cooled to 10 °C, stirred for 1 h and the observed solid material is collected by filtration. The filter cake is washed with water (1.00 L) and hexanes (2.00 L) and dried in vacuo at 40 to 45 'C to constant weight to yield the title compound (990.0 g, 78.2percent). A mixture of 300 mg of methyl 4-bromobenzo[b]thiophene-2-carboxylate, 100 mg of lithium hydroxide monohydrate, 3 ml of water, and 9 ml of methanol was stirred for 2 hours at 75°C. The reaction mixture was concentratedunder reduced pressure, water was added to the residues, and the residue was washed three times with tert-butyl methylether. Concentrated hydrochloric acid was added to the aqueous layer, and then extraction was performed three timesby using tert-butyl methyl ether. The collected organic layer was washed with saturated saline, dried over magnesiumsulfate, and then concentrated under reduced pressure, thereby obtaining 270 mg of 4-bromobenzo[b]thiophene-2-carboxylic acid (hereinafter, described as a 'compound 10 of the present invention). Compound 10 of the presentinvention 1H-NMR (DMSO-D6) δ: 13.79 (br s, 1H), 8.11 (dd, 1H, J = 7.8, 0.8 Hz), 7.97 (s, 1H), 7.73 (dd, 1H, J = 7.8, 0.8 Hz), 7.46(t, 1H, J = 7.8 Hz).

Molecular Weight:257.11
XLogP3:3.5
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:255.91936
Monoisotopic Mass:255.91936
Topological Polar Surface Area:65.5
Heavy Atom Count:13
Complexity:222
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes