6-Bromo-3-methyl-2,3-dihydro-1,3-benzoxazol-2-one

Scheme B2; To a solution of B2.1 (1 equiv., 23 mmol, 5.0 g) in acetone (230 ml) were successively added potassium carbonate (1.5 equiv., 35 mmol, 5.0 g) and iodomethane (1.2 equiv., General procedure: To a stirred solution of 5-Methylbenzo[d]oxazol-2(3H)-one (12.0 g, 80 mmol) in DMF (100 mL) was added potassium carbonate (16.7 g, 121 mmol) and methyl iodide (7.6 mL, 121 mmol) at room temperature. The resulting mixture was stirred for 16 h at room temperature. The reaction mass was diluted with ice-water (300 mL), and the precipitated product was filtered off and dried to afford 10 g (76%) of the title product as white solid. 1HNMR (400 MHz, CDCl3) delta 7.08 (d, J=8.0 Hz, 1H), 6.92 (dd, J=8.0 & 2.0 Hz, 1H), 6.79 (d, J=2.0 Hz, 1H), 3.39 (s, 3H), 2.42 (s, 3H); GC-MS (m/z) 163 (M)+.In a sealed-tube, to a stirred and nitrogen purged solution of step-2 Intermediate (4.0 g, 17.5 mmol), ethylboronic acid (1.94 g, 26.3 mmol) and potassium phosphate (7.45 g, 35.1 mmol) in 1, 4-dioxane (40 mL) was added dicyclohexyl(2?, 6?-diisopropoxy-[1, 1?-biphenyl]-2-yl)phosphine (0.819 g, 1.754 mmol) and PdOAc2 (0.39 g, 1.75 mmol). The resulting mixture was stirred at 100 C. for 2 h. The reaction mixture was cooled to room temperature and diluted with ethyl acetate (100 mL), filtered through Celite pad and residue was washed with ethyl acetate (100 mL). The filtrate was concentrated under reduced pressure and the crude product was purified by flash column chromatography (silica gel, hexane/ethyl acetate 9:1 as eluent) to afford 3.0 g (97%) as a white solid. 1HNMR (400 MHz, CDCl3) delta 7.07 (d, J=2.0 Hz, 1H), 7.03 (dd, J=8.0 & 2.0 Hz, 1H), 6.88 (d, J=8.0 Hz, 1H), 3.40 (s, 3H), 2.69 (q, J=7.5 Hz, 2H), 1.25 (t, J=7.5 Hz, 3H); GC-MS (m/z) 177 (M)+.General procedure: A suspension of 5-arylpyrrolidin-2-ones (4 or 5; 1 equiv), CuI (0.5 equiv), cesium carbonate (2 equiv), and the corresponding aryl bromide (1.0-1.2 equiv) in dioxane was placed under nitrogen atmosphere. The coupling ligand DMEDA (1 equiv) was added dropwise by using a syringe and the mixture was then stirred at r.t. for 36 h. At the end of the reaction, all insoluble salts deposited after cooling at r.t. were collected by filtration, and then washed with dichloromethane. The resulting filtrate was concentrated in vacuo and the residue was partitioned between water and EtOAc. The organic layer was then dried over Na2SO4 and concentrated under reduced pressure then purified by flash chromatography on prepacked silica gel columns (EtOAc/n-heptane) to afford pure compounds 52, 53, and 54.General procedure: A suspension of 5-arylpyrrolidin-2-ones (4 or 5; 1 equiv), CuI (0.5 equiv), cesium carbonate (2 equiv), and the corresponding aryl bromide (1.0-1.2 equiv) in dioxane was placed under nitrogen atmosphere. The coupling ligand DMEDA (1 equiv) was added dropwise by using a syringe and the mixture was then stirred at r.t. for 36 h. At the end of the reaction, all insoluble salts deposited after cooling at r.t. were collected by filtration, and then washed with dichloromethane. The resulting filtrate was concentrated in vacuo and the residue was partitioned between water and EtOAc. The organic layer was then dried over Na2SO4 and concentrated under reduced pressure then purified by flash chromatography on prepacked silica gel columns (EtOAc/n-heptane) to afford pure compounds 52, 53, and 54.

Molecular Weight:228.04
XLogP3:2
Hydrogen Bond Acceptor Count:2
Exact Mass:226.95819
Monoisotopic Mass:226.95819
Topological Polar Surface Area:29.5
Heavy Atom Count:12
Complexity:209
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes