5-Bromo-1-benzofuran

Light yellow liquid

To a solution of the product from Step A (8.4g) in benzene (50ML) was added POLYPHOSPHORIC acid (10G). The mixture was heated at reflux for 4 hrs. The reaction was cooled to 0°C and poured into ice water (80ML) and extracted with ether. The ether layer was washed with saturated sodium bicarbonate and brine, dried with MGS04, filtered and concentrated in vacuo to give 4.9g of crude product (85percent).To a solution ol the product from Step A (8.4 g) in benzene (50 ml) was added polyphosphoric acid (10 g). The mixture was heated at reflux lor 4 hrs. The reaction was cooled to 0 C. and poured into ice water (80 ml) and extracted with ether. The ether layer was washed with saturated sodium bicarbonate and brine, dried with MgSO4, filtered and concentrated in vacuo to give 4.9 g ol crude product (85percent)To a solution of the product from Step A (8.4 g) in benzene (50 ml) was added polyphosphoric acid (10 g). The mixture was heated at reflux for 4 hrs. The reaction was cooled to 0 C. and poured into ice water (80 ml) and extracted with ether. The ether layer was washed with saturated sodium bicarbonate and brine, dried with MgSO4, filtered and concentrated in vacuo to give 4.9 g of crude product (85percent)Step B; To a solution of the product from Step A (8.4g) in benzene (50ml) was added polyphosphoric acid (10g). The mixture was heated at reflux for 4 hrs. The reaction was cooled to 0°C and poured into ice water (80ml) and extracted with ether. The ether layer was washed with saturated sodium bicarbonate and brine, dried with MgS04, filtered and concentrated in vacuo to give 4.9g of crude product (85percent)To a solution of the product from Step A (8.4g) in benzene (50mut) was added polyphosphoric acid (10g). The mixture was heated at reflux for 4 hrs. The reaction was cooled to 0°C and poured into ice water (80ml) and extracted with ether. The ether layer was washed with saturated sodium bicarbonate and brine, dried with MgS04, filtered and concentrated in vacuo to give 4.9g of crude product (85percent)General procedure: A 25 mL round-bottomed flask was charged with 2-aryloxyacetaldehyde diethyl acetals (1 mmol), Sn-b (0.1 g), andtrifluorotoluene (10 mL). The mixture was stirred under refluxingcondition and monitored by GC. Upon completion, the mixture wascooled to room temperature, and the catalyst Sn-b was filtrate off.The filter cake was washed with trifluorotoluene (10 mL3). Thecombined filtratewas concentrated under vacuum. The residuewaspurified by flash column chromatography on SiO2 (petroleumether/ethyl acetate) to afford the desired 2, 3-unsubstituted benzo[b]furans.Step 2.Phosphoric acid (40 g) was added to a solution of l-bromo-4-(2, 2-diethoxyethoxy)benzene (51.9 mmol) in chlorobenzene (80 mL) and the reaction mixture was heated at reflux for 16 h. The reaction mixture was allowed to cool to rt and the chlorobenzene layer was decanted. The residue was washed with toluene (2 x 30 mL) and the combined organic layers were concentrated. The residue was purified by Flash chromatography (hexane) to provide 5-bromobenzofuran in 50percent yield as colorless oil.2. Synthesis of 5-bromobenzofuran.Phosphoric acid (40 g) was added to a solution of l-bromo-4-(2, 2- diethoxyethoxy)benzene (51.9 mmol) in chlorobenzene (80 mL) and the reaction mixture was heated at reflux for 16 h. The reaction mixture was allowed to cool to rt and the chlorobenzene layer was decanted. The residue was washed with toluene (2 x 30 mL) and the combined organic layers were concentrated. The residue was purified by Flash chromatography (hexane) to provide 5-bromobenzofuran in 50percent yield as colorless oil.2. Synthesis of 5-bromobenzofuran.Phosphoric acid (40 g) was added to a solution of l-bromo-4-(2, 2- diethoxyethoxy)benzene (51.9 mmol) in chlorobenzene (80 mL) and the reaction mixture was heated at reflux for 16 h. The reaction mixture was allowed to cool to rt and the chlorobenzene layer was decanted. The residue was washed with toluene (2 x 30 mL) and the combined organic layers were concentrated. The residue was purified by Flash chromatography (hexane) to provide 5-bromobenzofuran in 50percent yield as colorless oil.A mixture of l-bromo-4-(2, 2-dimethoxyethoxy)benzene (200 mmol) and polyphosphoric acid (30 mL) was heated to 100 °C and stirred overnight. The reaction mixture was cooled to room temperature and poured into aqueous sodium carbonate until the pH was ~7 to 8. Then the mixture was extracted with dichloromethane (4 x 100 mL) and the organic layers were combined, washed with water (100 mL) and saturated brine (100 mL), dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The mixture was distilled under reduced pressure (95 °C, 5 mm Hg) to give a clear oil as the title product (25percent). Chlorobenzene (1200 mL) was added to a 5000 mL three-necked bottomed flask and the crude crude 1-bromo-4 '- (2, 2-dimethoxyethyl) benzene (350 g) (870 g).Stirring was started and heated to reflux for 28 hours.TLC and GC tracking reactions.After completion of the reaction, the reaction solution was cooled to room temperature and the lower layer was separated.The organic phase was washed with water (600 mL) and sodium hydroxide (2 mol / L, 600 mL).Dried over sodium sulfate overnight.Distillation to remove most of the chlorobenzene.The crude product 5-bromobenzofuran (245 g) was then distilled under reduced pressure.After the distillation of pure 5-bromobenzofuran 179 g, the yield of 74.9percent.To a mixture of 2-formyl-4-bromophenoxy acetic acid [(50G, ] 0. [192MOL), ] sodium acetate [(100G, ] 1. 21mol) in acetic acid (250mL) at [100°C] was added acetic anhydride [(LOOML)] portions during a period of 3h. The reaction mixture was then refluxed for 20h. The solvent was removed by distillation and residue diluted with 3N HCl [(500ML)] and refluxed for 2h. The reaction mixture was then concentrated under vacuum and product extracted with pet. ether [(3X200ML).] The organic layer was washed with 10percent [NAHC03] solution and evaporated to give [5-BROMO-1-BENZOFURAN] [(15G, ] 40percent) as a pale yellow liquid.

Molecular Weight:197.03
XLogP3:3
Hydrogen Bond Acceptor Count:1
Exact Mass:195.95238
Monoisotopic Mass:195.95238
Topological Polar Surface Area:13.1
Heavy Atom Count:10
Complexity:126
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes