Acetic Acid → Benzenamine, 4-fluoro-N-(1-methylethyl)-

Participants

Reaction Steps

To a stirring solution of 17 mL (180 mmol) of 4-fluoroaniline in 550 mL of THF at RT is added 26.7 mL (180 mmol, 1.0 equiv) of acetone, 10.3 mL (180 mmol, 1.0 equiv) acetic acid, and 57.22 g (270 mmol, 1.5 equiv) of sodium triacetoxyborohydride. The solution is stirred at RT for 15 h, cooled to 0° C., and then quenched by addition of H2O. The reaction mixture warmed to RT and is poured into EtOAc, the organic layer is separated, washed with brine (1×200 mL), dried (MgSO4) and the solvents removed in vacuo. Purification of the material by silica gel flash column chromatography using EtOAc/hexane 1:1 as eluent afforded 14.9 g (54%) of (4-Fluoro-phenyl)-isopropyl amine. A solution of 6.68 g (43.6 mmol) of (this material in 50 mL of DCM is cooled to 0° C. and 6 mL (43.6 mmol, 1.0 equiv) triethyl amine is added, followed by dropwise addition of 2.27 mL (43.6 mmol, 1.0 equiv) of bromoacetyl bromide. The solution is stirred at RT for 15 h and then poured into DCM (200 mL). The organic layer is separated, washed with saturated aq NaHCO3 (4×50 mL), 1N HCl (6×50 mL), brine (1×50 mL), dried (MgSO4) and the solvents removed in vacuo. Purification of the material by silica gel flash column chromatography using EtOAc/hexane (3:17) as eluent afforded 5.32 g of 2-Bromo-N-(4-fluoro-phenyl)-N-isopropyl-acetamide: 1HNMR (CDCl3, 300 MHz) δ7.26-7.09 (m, 4H), 4.85 (m,1H), 3.51 (s, 2H), 1.05 (d, 6H, J=6.9); low resolution MS(FAB) m/e 274 (MH+).

Provenance & Evidence