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

Participants

Reaction Conditions

Reaction Steps

A mixture of 5-bromo-2-chloroaniline (1.09 g, 5.29 mmol), 2-dicyclohexylphosphino-2,4,6,-triisopropylbiphenyl, (X-Phos) (202 mg, 0.42 mmol), tris(dibenzylideneacetone)dipalladium (0) (198 mg, 0.22 mmol), and morpholine (2.3 mL, 26.4 mmol) in dry THF (12 mL) was degassed by nitrogen. To this mixture was added lithium bis(trimethylsilyl)amide, 1.0M in THF (25.0 mL, 25.0 mmol) dropwise, and the resulting reaction was heated to 60° C. After 2.5 h, the reaction was cooled to rt then poured into water. After extracting twice with EtOAc and twice with DCM, the combined organic layers were dried over anhydrous magnesium sulfate. After filtration and concentration, the residue was purified on silica gel (0-45% EtOAc in hexanes) to yield 2-chloro-5-morpholinoaniline. 1H NMR (400 MHz, CDCl3) δ ppm 7.12 (1H, d, J=8.6 Hz), 6.42 (2H, m), 4.00 (2H, br. s.), 3.93 (4H, m), 3.22 (4H, m).

Provenance & Evidence