2-Nitroethanol → 6-Bromo-3-nitro-chroman

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6-Bromo-chroman-3-ylamine was prepared according to the literature procedure described by Andersson, B. R. et al. WO9012795. Thus, a mixture of 5-bromosalicylaldehyde (9.5 g, 47 mmol), di-n-butylammonium chloride (3.8 g, 23 mmol), and 2-nitroethanol (6.8 g, 75 mmol) in amyl acetate (60 mL) was heated at reflux for 3 hours with a Dean-Stark apparatus under nitrogen atmosphere. The solvent was removed in vacuo and the product was dissolved in CH2Cl2 (280 mL) followed by the addition of NaCNBH3 (9.6 g, 150 mmol). The mixture was stirred for 30 minutes and water (100 mL) was added to quench the reaction. The organic layer was separated and the aqueous layer was extracted with CH2Cl2 (50 mL×3). The combined organic layers were washed with brine, dried (Na2SO4), and concentrated in vacuo. The crude product was chromatographed on silica gel by eluting with 1:1 hexane/CH2Cl2 to give 4.4 g (40%) of pure 6-bromo-3-nitro-chroman as a light yellow solid. 1H NMR (300 MHz, CDCl3): δ 7.18 (m, 2H), 6.68 (d, J=8.4 Hz, 1H), 4.88 (m, 1H), 4.62 (m, 1H), 4.32 (m, 1H), 4.47 (m, 1H), 3.28 (dd, J=17.4, 6.0 Hz, 1H).

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