Morpholine → 2-Chloro-5-(morpholin-4-yl)aniline

Participants

Reaction Conditions

Reaction Steps

A mixture of 5-bromo-2-chloroaniline (2.0 g, 9.74 mmol), morpholine (4.3 mL, 49 mmol), 2-dicyclohexylphosphino-2,4,6,-triisopropylbiphenyl, (X-Phos) (0.37 g, 0.79 mmol), and tris(dibenzylideneacetone)dipalladium (0) (0.37 g, 0.4 mmol) in dry THF (20 mL) was degassed by nitrogen. To this mixture was added 1.0M lithium bis(trimethylsilyl)amide in THF (54 mL) dropwise, and the resulting reaction was heated to 60° C. After 2 h, the reaction was cooled to rt then cond under reduced pressure to ˜5 mL. After pouring into water, the mixture was extracted twice with EtOAc and twice with DCM. After the combined organic layers were dried over anhydrous magnesium sulfate, filtration, and concentration, the residue was purified on silica gel (0-30% EtOAc in hexanes) to yield 2-chloro-5-morpholinoaniline. 1H NMR (400 MHz, CDCl3) δ ppm 7.19 (1H, m), 6.41 (2H, m), 4.00 (2H, br. s.), 3.93 (4H, m), 3.22 (4H, m).

Provenance & Evidence