5-BROMO-2,2-DIMETHYL-1,3-BENZODIOXOLE

2, 2-dimethyl-2H-1 , 3-benzodioxole Ex.102a (1.00 g, 6.66 mmol) wasdissolved in dry DMF (20 mL). N-bromosuccinimide (1.19 g, 6.66 mmol) was added portionwise at rt. The mixture was then stirred overnight at this temperature. LCMS showed almost complete consumption of the starting material. The reaction was found to be difficult to monitor by TLC as starting material and product showed the same Rf. The mixture was diluted with water, some brine was added followed by EtOAc. The two phases were separated, the organic layer was dried over MgSO4, filtered and the solution was conentrated to dryness. The crude oil was purified by silica gel column chromatography eluting with Cyclohexane/EtOAc [95:5]. The product fractions were combined and concentrated to dryness to afford 5-bromo-2, 2-dimethyl- 2H-1, 3-benzodioxole Ex.102b (1.32 g, 86percent) as colourless oil. 1H NMR (300 MHz, DMSO-d6, din ppm): 1.63 (s, 6H), 6.79 (d, 1H, J=8.lHz), 6.95 (dd, 1H, J=8.lHz, J=2.lHz), 7.06 (d, 1H, J=2.lHz)To an ice-cooled solution of 4-bromoveratrole (23.0 mmol) in dichloromethane (10 mL) was added boron tribromide dropwise (34.5 ml_ of a 1 M solution in dichloromethane). The reaction mixture was stirred at reflux for 18 h and then cooled and treated with ice and 6N aqueous sodium hydroxide solution (10 mL). The layers were separated, and the aqueous layer was acidified with 6N aqueous hydrochloric acid solution and extracted with diethyl ether. Concentration of the ether layer provided the crude diol intermediate, which was dissolved in toluene (30 mL) and treated with 2, 2-dimethoxypropane (28 mmol) and phosphorus pentoxide (0.023 mmol). The reaction mixture was heated at 90 0C for 4 h. The cooled reaction mixture was washed with saturated aqueous sodium carbonate solution and brine and then concentrated in vacuo. Purification of the residue by flash chromatography (5-60percent ethyl acetate/hexanes) provided the intermediate 5-bromo-2, 2- dimethyl-1 , 3-benzodioxole in 44percent yield. 1H NMR (400 MHz, CDCI3): δ 6.93-6.82 (m, 2H), 6.63-6.60 (m, 1 H), 1 .69 (s, 6H). A solution of 5-bromo-2, 2-dimethyl-1 , 3-benzodioxole (2.6 mmol), 4-(4, 4, 5, 5- tetramethyl-1 , 3, 2-dioxaborolan-2-yl)aniline (3.1 mmol), and tetrakis(triphenylphosphine)palladium(0) (0.26 mmol) in acetonitrile (2.6 mL) and 2M aqueous sodium carbonate solution (2.6 mL) was irradiated in a Personal Chemistry Emrys Optimizer microwave at 150 0C for 500 s. The reaction mixture was filtered and concentrated in vacuo. The pure title product was isolated upon precipitation using 80:20 diethyl ether/hexanes (31 percent). ESMS [M+H]+: 242.0.Preparation 59 2, 2-dimethyl-2H-1 , 3-benzodioxole Ex.102a (1.00 g, 6.66 mmol) wasdissolved in dry DMF (20 mL). N-bromosuccinimide (1.19 g, 6.66 mmol) was added portionwise at rt. The mixture was then stirred overnight at this temperature. LCMS showed almost complete consumption of the starting material. The reaction was found to be difficult to monitor by TLC as starting material and product showed the same Rf. The mixture was diluted with water, some brine was added followed by EtOAc. The two phases were separated, the organic layer was dried over MgSO4, filtered and the solution was conentrated to dryness. The crude oil was purified by silica gel column chromatography eluting with Cyclohexane/EtOAc [95:5]. The product fractions were combined and concentrated to dryness to afford 5-bromo-2, 2-dimethyl- 2H-1, 3-benzodioxole Ex.102b (1.32 g, 86%) as colourless oil. 1H NMR (300 MHz, DMSO-d6, din ppm): 1.63 (s, 6H), 6.79 (d, 1H, J=8.lHz), 6.95 (dd, 1H, J=8.lHz, J=2.lHz), 7.06 (d, 1H, J=2.lHz)

Molecular Weight:229.07
XLogP3:3
Hydrogen Bond Acceptor Count:2
Exact Mass:227.97859
Monoisotopic Mass:227.97859
Topological Polar Surface Area:18.5
Heavy Atom Count:12
Complexity:181
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes