METHYL5-BROMO-2-FUROATE

White to slightly yellow crystalline powder

Weigh 950 mg (5.00 mmol) of 5-bromo-2-furoic acid in 10 mL of MeOH, slowly add 2 mL of SOCl2, After the end of the reaction, the mixture was cooled to room temperature, evaporated to dryness under reduced pressure and dissolved in a certain amount of toluene, Repeatedly 3 times to get the intermediate5-bromo-2-furoate methyl ester, yield 100percent.Compound 3 (5 . 37 g, 30 mmol) dissolved in 200 ml of methanol in the solvent, by adding 6 ml of concentrated sulfuric acid, the temperature to 70 degree Celsius reaction 6 hours, concentrated under reduced pressure to remove the solvent, is added to the remaining reaction mixture in 200 ml of ice water, and saturated sodium carbonate solution to adjust the pH to 7 - 8, ethyl acetate extraction reaction solution three times, the combined organic phase after washing with saturated sodium chloride solution, dried with anhydrous sodium sulfate. The solvent is removed under reduced pressure, vacuum drying to obtain compound 4 a (5 . 66 g, 27.6 mmol), yield 92percent.Concentrated sulfuric acid (0.56 mL, 10.5 1 mmol) was added dropwise to a solution of carboxylic acid (9) (20.0 g, 0. 105 mol) in methanol ( 1 050 mL) at room temperature. The solution was heated at reflux for 1 7 hours. The solution was allowed to cool to room temperature and the methanol was removed under reduced pressure. The residue was diluted with water and the pi 1 of the solution was adjusted to pi 1 9 using solid sodium bicarbonate. The mixture was extracted with ethyl acetate (x 3). The organic extracts were combined and washed with water and brine, then dried The solvent was removed under reduced pressure to afford the product 8 as a white solid ( 19.47 g, 9 1 percent), which was of sufficient purity to use in the next step, with all analytical data matching that reported in the literature (Y. Zhu , H. Yan , L. Lu , D. Liu , G. Rong , J. Mao J. Org. Chem. , 2013, 78, 9898-9905). Mp 67 - 68 °C; NMR (300 MHz; CDC1A solution of 5-bromo-2-furoic acid (1.00 g, 5.2 mmol) in dichloromethane (50 mL) was treated at 0°C with oxalyl chlorid 7.8 mmol) and a catalytic amount of N, N- dimethylformamide (125 25 minutes, MeOH (2 mL) was added to the solution and stirred at ambient temperature for one night. The solvent and excess of oxalyl chloride were removed under reduced pressure and the solid was dissolved in EtOAc. The organic layer was washed with a 1M NaOH solution, dried over NaIntermediate 4: Methyl 5-BROMO-2-FUROATE Method A A mixture of dichloromethane (700 mL), 5-bromo-2-furoic acid (146 g, 764 MMOL), 1, 8-DIAZABICYCLO [5.4. 0] undec-7-ene (DBU; 122 G, 801 MMOL), and iodomethane (130 g, 916 MMOL) was heated under reflux for 22 hours. The mixture was allowed to cool to 20°C and was then successively washed with a saturated aqueous ammonium chloride solution (300 mL), A saturated aqueous sodium hydrogen carbonate solution (300 mL), and water (300 mL). The organic layer was separated and the aqueous wash solutions were extracted with ethyl acetate (2 x 200 mL) in the same order as they had been used for workup. All organic extracts were combined and dried over anhydrous sodium sulphate, the solvent was removed under reduced pressure (rotary evaporator; 800 to 150 mbar, 40°C), and the residue was dried in vacuo (10 mbar, 20°C, 30 minutes). n-Hexane (1.1 L) was added to the residue and the resulting mixture was heated under reflux for 5 minutes, followed by filtration of the hot mixture. The filter cake was washed with boiling n-hexane (160 mL), the filtrate and wash solution were combined, and. the resulting solution was allowed to cool to 20°C within 2 hours and was then kept undisturbed at 4°C for 2 days (formation of a crystalline precipitate). The solid was separated by decantation and recrystallised from boiling n-hexane (720 mL; CRYSTALLISATION at 4°C over a period of 4 days). The product was again isolated by decantation and dried in vacuo (0.01 mbar, 20°C, 4 hours) to give 112 g of-a yellowish crystalline solid. The mother LIQUOURS of the crystallisation steps were combined and concentrated to 250 ML (rotary evaporator, 300 mbar/40°C), and a further 17 g of the product were obtained by crystallisation using the same method as described above. The title compound was obtained in a total yield of 82percent as a YELLOWISH CRYSTALLINE SOLID (129 G, 629 MMOL) ; mp 64-65°C. Anal. CALCD for C6H5BRO3 : C, 35.15 ; H, 2.46 ; Br, 38.98. Found: C, 35.4 ; H, 2.7 ; Br, 38.8.In a Schlenk tube successively charged with 5-bromo-furan-carboxylic acid (0.3mmol), potassium bromide (0.09mol), and N, N- dimethylformamide (2mL), with micro-injector was added dimethyl malonate ester (1.8mmol), the system was sealed in a 130 ° C oil bath was heated with stirring for about 12 hours, after the completion of the reaction, 4mL of water was added to quench the reaction, and then extracted with ethyl acetate (10 mL × 3), the combined organic phase was dried over anhydrous sodium sulfate, and concentrated by a simple column chromatography (eluent petroleum ether (60-90 ° C)), to give the product 5-bromo-furan carboxylic acid methyl ester, 90percent yield.

Molecular Weight:205.01
XLogP3:1.8
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:2
Exact Mass:203.94221
Monoisotopic Mass:203.94221
Topological Polar Surface Area:39.4
Heavy Atom Count:10
Complexity:137
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes