6-BROMO-BENZO[B]THIOPHENE-2-CARBOXY LIC ACID METHYL ESTER

General procedure: To a stirred solution of compound 1a or 1b(9.90 mmol)in DMF(20 mL) was added methyl thioglycolate (10.9 mmol) and potassiumcarbonate (39.6 mmol). The resulting mixture was stirred at60 °C for 15 h. The DMF was removed under reduced pressure, water (50 mL) was added and the mixture was extracted with ethylacetate (2 x 40 mL). The combined organic layers were dried withsodium sulfate, filtered, and the solvents were removed underreduced pressure to afford the title compound 2a or 2b.TEA (1.29g, 12.85mmol) and mercapto-acetic acid methyl ester (1.14 g, 10.83mmol) were added to acetonitrile (50mL) previously purged with argon (10 minute). This was followed by the addition of 4-bromo-2-fluoro-benzaldehyde (2g, 9.852mmol) and the resulting mixture was heated to reflux at 85°C overnight. The reaction was monitored by TLC (20percent ethyl acetate in hexane). The reaction mixture was cooled, concentrated, basified with 10percentNaOH solution and extracted with ethyl acetate to afford the crude product. Purification by column chromatography on silica gel (5percent ethyl acetate in hexane) afforded 2.4g of the product (90percent yield).1H NMR (CDC14-Bromo-2-fluorobenzaldehyde (808 mg, 4.00 mmol) was dissolved in dimethylsulfoxide (5.00 mL)Methyl mercaptoacetate (375 μL), Triethyl amine (1.5 mL) was added, And the mixture was stirred at 80 ° C. for 3 hours.20 mL of purified water was added, and the precipitated white solid was collected by filtration, And washed with purified water to obtain Compound 8 in a yield of 700 mg (yield 64.8percent).To a solution of 4-bromo-2-fluorobenzaldehyde (10 g, 49 mmol) and methyl 2- mercaptoacetate (7.8 g, 74 mmol) in dimethylsulfoxide (100 mL) was added potassium carbonate (13 g, 99 mmol) portionwise at room temperature. The resulting mixture was stirred at 70 °C for 3 hours. On completion, the mixture was poured into ice-water, resulting in formation of a solid. The mixture was stirred for 30 min., and the solid was collected by filtration, washed with water and dried in vacuo. The residue was purified by silica gel chromatography [petroleum ether: ethyl acetate = 7: 1] to give compound B-110 (8.1 g, 61percent yield) as a white solid.The literature procedure of Fedi et al.3.76 g (35.5 mmol) of methyl mercaptoacetate are slowly added dropwise to a suspension of 1.93 g (48.3 mmol) of sodium hydride (as 60percent suspension in mineral oil) in 65 ml of DMSO at room temperature. After hydrogen evolution ceases, a solution of 6.54 g (32.2 mmol) of 4-bromo-2-fluorobenzaldehyde in 10 ml of DMSO is added. After 10 min, the reaction mixture is stirred into 200 ml of ice-water, and the resulting precipitate is isolated. The solid is washed twice with water and dried in vacuo at 50° C. 4.06 g (46.4percent of theory) of the title compound are obtained.

6-Bromobenzo[b]thiophene-2-carboxylic acid methyl ester is used in the synthesis of benzothiophene derivatives as histone deacetylase inhibitors.

Molecular Weight:271.13
XLogP3:3.8
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:2
Exact Mass:269.93501
Monoisotopic Mass:269.93501
Topological Polar Surface Area:54.5
Heavy Atom Count:14
Complexity:234
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes