6-Bromo-1,2-benzisoxazol-3(2H)-one

(12) A solution of , Γ-earbonyidiimidazoie (2.0 eq) in THF (0, 1 M) was added dropwise to a rcfluxing solution of 4-bromo~2~hydroxy~be:nzertecari ohydfoxar)iie acid (1.0 eq) in THF (0.15 M) and then stirred for 2h at reihrxing conditions. The THF was removed under vacuum and the residue was suspended ia water. HO (2 ) was added dropwise at rt. A precipitate formed and was collected by filtration, washed with water and dried overnight ia a vacuum ovea to afford 6-bromo- 1 , 2-benzoxazol- 3-0.1 (95percent yield).General procedure: Salicylhydroxamic acid 1a (77 mg, 0.5 mmol, 1 equiv) was dissolved in anhydrous THF (7 mL) under an inert (NStep A: 6-bromobenzo[d]isoxazol-3-ol: N-hydroxyacetamide (0.99 g, 12.9 mmol) was dissolved in DMF (20 mL). To this was added KOt-Bu (1.44 g, 12.9 mmol) and the reaction was stirred for 30 minutes before addition of methyl 4-bromo-2-fluorobenzoate (2.0 g, 8.58 mmol). The reaction mixture was stirred at ambient temperature for 10 days, then diluted with ethyl acetate (50 mL) and 1N NaOH (50 mL). The aqueous layer was washed with ethyl acetate, then acidified with 2N HCl (30 mL). The desired product was collected by filtration (570 mg, 31percent).(17) To a suspension of pyridine (3.0 eq) and 6-brorao-l 2-benzoxaaol-3-ol (1.0 eq) in DCM (0, 05 M) at 0'C under nitrogen was added triflooromethanesoifonic anndride (1 , 5 eq, 1 M in DCM), dropwise. After 10 rain, the ice bath was removed, it was stirred for an additional 45 rain at rt.Rxti was added to DCM: Water (1 : i ), The organic layer was separated with the hydrophobic phase separator, solvent was removed and the product (6-brorao-i , 2-benzoxazol-3-yl ) trifluororaedianesulfonate was carried forward without further purification.(13) 6-bron .li2-benzoxazoi-3-ol (L0 eq), potassium carbonate f 1.5 eq) were added to a bf, followed by DMF (0.2 M). 4-Methoxybeayl chloride ( i.l eq) was added and the rxn was stirred overnight at rt. LCMS shows both product regioisoraers, Rxn is added to water (0.1 M) and extracted with EtO Ac (2x). The combined extracts are washed with water (3x), brine, and dried over MgSO.*. Solvent was removed in vacuo and the residue was purified by normal phase chromatography ( 15-30%EiOAciiexaoes). The two regioisomers were collected separately. The major product, 6-bronio-3-{(4- methoxyphenyl }methoxy] 1 , 2-benzoxazo e (39% yield)and the minor product 6~bromo-2-i(4~methoxyphenyl)methyl'j-l, 2-benzoxazol-3-one (.15% yield).Step A: An ice-bath cooled solution of 6-brom-1, 2-benzisoxazol-3 (2H)-one (Intermediate 24) (0.05g) and dry pyridine (0. 05ml) in dry dichloromethane (4ml) was stirred under nitrogen and treated with triflic anhydride (60pal). The solution was stirred at room temp. for 4h, diluted with cyclohexane then applied to a Varian Bond-Elut SPE cartridge (silica, lg) and eluted with dichloromethane to give a yellow oil. The oil was dissolved in acetonitrile (2ml) treated with 1, 1-dimethylethyl 1-piperazinecarboxylate (0.04g) and diisopropylethylamine (0. 05ml) then stirred at 70 under nitrogen for 20h. The cooled reaction mixture was purified on a Varian Bond-Elut SPE cartridge (silica, 5g) using dichloromethane: methanol to give the title compound as a white solid (0.016g). LCMS: Rt 3. 62min.An ice-bath cooled solution of 6-brom-1, 2-benzisoxazol-3 (2H)-one (Intermediate 24) (0. 15g) and dry pyridine (0. 15ml) in dry dichloromethane (12ml) was stirred under nitrogen and treated with triflic anhydride (18011L). The solution was stirred at room temp. for 90min, diluted with cyclohexane then applied to a Varian Bond-Elut SPE cartridge (silica, 5g) and eluted with cyclohexane and dichloromethane to give a colourless oil. The oil was dissolved in acetonitrile (4ml) treated with morpholine (61 , ut) and diisopropylethylamine (0. 15ml) then stirred at 70 under nitrogen for 16h. The cooled reaction mixture was purified on a Varian Bond-Elut SPE cartridge (silica, 5g) using dichloromethane: ethanol : 0. 88ammonia to give the title compound as a white solid (0.03g). LCMS: Rt 3. 01min.Step B: tert-butyl 6-bromo-3-oxobenzo[d]isoxazole-2(3H)-carboxylate: To a suspension of

Molecular Weight:214.02
XLogP3:1.8
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Exact Mass:212.94254
Monoisotopic Mass:212.94254
Topological Polar Surface Area:38.3
Heavy Atom Count:11
Complexity:185
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes