Potassium Carbonate → 3-(2-Bromopyridin-3-yl)-5-nitro-3,4-dihydro-2H-1,4-benzoxazin-3-ol

HRID 589103Notes

Reaction equation

Br[CH2:2][C:3]([C:5]1[C:6]([Br:11])=[N:7][CH:8]=[CH:9][CH:10]=1)=[O:4].C(=O)([O-])[O-].[K+].[K+].[NH2:18][C:19]1[C:24]([N+:25]([O-:27])=[O:26])=[CH:23][CH:22]=[CH:21][C:20]=1[OH:28]>C(Cl)Cl.O.CCCC[N+](CCCC)(CCCC)CCCC.[Br-].[Cl-].[Na+].O>[Br:11][C:6]1[C:5]([C:3]2([OH:4])[NH:18][C:19]3[C:24]([N+:25]([O-:27])=[O:26])=[CH:23][CH:22]=[CH:21][C:20]=3[O:28][CH2:2]2)=[CH:10][CH:9]=[CH:8][N:7]=1

Participants

Conditions

Temperature: 40 °C

Procedure

A solution of 2-bromo-1-(2-bromopyridin-3-yl)ethanone (2.15 g, 7.71 mmol) in methylene chloride (77.1 mL) and water (19.3 mL) was treated with potassium carbonate (2.13 g, 15.4 mmol), tetra-N-butylammonium bromide (500 mg, 1.50 mmol), and 2-amino-3-nitrophenol (1.31 g, 8.48 mmol), and heated at 40° C. for 5 h. The reaction mixture was then diluted with brine. The aqueous layer was separated and extracted with dichloromethane (2×100 mL). The combined organic layers were washed with water and brine, dried over magnesium sulfate, filtered, and concentrated to give the crude product. Purification by flash column chromatography (100% hexanes to 35% ethyl acetate/hexanes) gave the desired product (2.45 g, 90%) as a racemic mixture. LCMS calculated for C13H11BrN3O4 (M+H)+: m/z=352.0, 354.0. found: 351.7, 353.8.

Workup

customThe aqueous layer was separated
extractionextracted with dichloromethane (2×100 mL)
washThe combined organic layers were washed with water and brine
dry with materialdried over magnesium sulfate
filtrationfiltered
concentrationconcentrated
customto give the crude product
customPurification by flash column chromatography (100% hexanes to 35% ethyl acetate/hexanes)

Sources & evidence

ORD record: ord-a8b08553725640e6aadc839e1a075c85
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09227985B2

Reaction notes

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