METHYL 3-BROMOTHIOPHENE-2-CARBOXYLATE

Off-white solid

3-amino-2-thiophenecarboxylic acid methyl ester (100 g, 0.6369 mol) was suspended in hydrobromic acid (220 ml), and the mixture was stirred at room temperature for 15 mm. The mixture was cooled to 0-5°C, and sodium nitrite (46.0 g, 0.666 mol) in water (100 ml) was added dropwise below 5°C. The mixture was stirred for lhr, and then was addedto a copper (I) bromide (96.0 g, 0.6692 mol) in hydrobromic acid (260 ml) at room temperature. The resulting mixture was stirred at 60-65°C for 2 hrs. The reaction mixture was diluted with 1200 ml of water while maintaining at 25-30°C by cooling and extracted with two 600 ml portions of ethyl acetate. The ethyl acetate extracts were combined, washed two times with 600 ml portions of water, and dried over anhydrous sodiumsulfate. The ethyl acetate was removed by distillation under vacuum at 60°C to give 129.0g (91.6 percent) as a yellow solid, melting point 47°C to 48°C, with 96percent purity by HPLC.‘HNMR (400 MHz, CDC13) 6- Value (ppm): 3.90(s, 0-CR3, 3H), 7.09 (d, 1H), 7.46 (d, 1H).13 CNMR (400 MHz, CDC13) 6- Value (ppm): 52.10(1C), 116.96(1C), 127.12(1C), 130.61 (1C), 133.63 (1C), 161.0 (1C). Mass: 222.8 [M+1].General procedure: Anhydrous copper bromide (12mmol), tert-butyl nitrite (15mmol), and anhydrous acetonitrile (40mL) were added at 0 Copper bromide (6.7 g, 30.0 mmol) and t-butyl nitrite (3.57 ml, 30 mmol) were dissolved in acetonitrile (40 ml) A solution of methyl 3-amino-2-carboxylate (3.14 g, 20.0 mmol) After overnight reaction at room temperature, Then heated to 60 ° C for 1 hour, After completion of the reaction, cooled to room temperature, quenched by the addition of 2N HC1, add water, extracted with ethyl acetate, combined with several layers, dried and evaporated to dryness, the product was purified by a rapid preparative column 3.32g, yield 75percent.A mixture of S-bromo-thiophene-l-carboxylic acid (2.2g, lO.βmmol), 4N HCl (in dioxane, ImI), H2SO4 (98percent, 0.2ml) and methanol (30ml) was heated under reflux for 24h, cooled to room temperature, diluted with ethyl acetate, washed withwater, aq. NaHCO3, half- sat.-aq. NaCl twice, dried (MgSO4) and concentrated to dryness to give compound 23G (100percent) directly used in next step.By refluxing 3-bromothiophene-2-carboxylic acid and trimethylsilyl chloride (TMSCI) in a methanol solvent for 12 hours, 3-bromothiophene-2-carboxylic acid methylester was prepared. Yield: 87percent White solid

Molecular Weight:221.07
XLogP3:2.5
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:2
Exact Mass:219.91936
Monoisotopic Mass:219.91936
Topological Polar Surface Area:54.5
Heavy Atom Count:10
Complexity:140
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes