Stannous chloride dihydrate → 3-Bromo-4-(3-methyloxetan-3-yl)aniline

Temperature

70 °C

To a solution of 2-(2-bromo-4-nitrophenyl)-2-methylpropane-1,3-diol (7.2 g, 24.82 mmol) in anhydrous benzene (75 mL) was added cyanomethylenetributylphosphorane (9.0 g, 37.29 mmol) at room temperature. The reaction mixture was stirred for 72 h, then evaporated to dryness and re-dissolved in ethanol (100 mL). Tin (II) chloride dihydrate (28 g, 94.42 mmol) was then added and the resulting solution was heated to 70° C. for 1 hour. The reaction mixture was cooled to room temperature and then quenched with a saturated aqueous solution of sodium bicarbonate. The reaction mixture was then extracted three times with ethyl acetate. The combined organic layers were dried over anhydrous Na2SO4 and evaporated under vacuum to give the crude product, which was purified by reverse phase HPLC to afford 3-bromo-4-(3-methyloxetan-3-yl)aniline (1.5 g, 18%) TFA salt. 1H NMR (400 MHz, CD3CN) δ 6.93 (d, J=2.4 Hz, 1H), 6.78 (d, J=8.4 Hz, 1H), 6.71 (dd, J=2.4, 8.4 Hz, 1H), 4.94 (d, J=5.6 Hz, 2H), 4.46 (d, J=6.0 Hz, 2H), 1.70 (s, 3H).

1. customevaporated to dryness
2. dissolutionre-dissolved in ethanol (100 mL)
3. temperatureThe reaction mixture was cooled to room temperature
4. customquenched with a saturated aqueous solution of sodium bicarbonate
5. extractionThe reaction mixture was then extracted three times with ethyl acetate
6. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
7. customevaporated under vacuum
8. customto give the crude product, which
9. customwas purified by reverse phase HPLC

ORD record

ord-bd15c2021f8042bdaf02447269ad9cea

Source dataset

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08614327B2