Tetrahydrofuran → 1-[5-(2,2-Dimethyl-propyl)-isoxazol-3-yl]-ethylamine

Participants

Reaction Steps

The solution of 5-(2,2-dimethyl-propyl)-isoxazole-3-carbonitrile ([943925-83-5] 16 g, 97.5 mmol) in THF (160 ml) was cooled in an ice bath and under an atmosphere of nitrogen methylmagnesium chloride (3 M solution in THF, 51 ml, 127 mmol) was added slowly so that the reaction temperature did not rise above 10° C. The reaction was stirred for 1 h at rt. LiAlH4 (1 M solution in THF, 110 ml, 110 mmol) was added over 10 min keeping the reaction temperature below 40° C. The reaction was heated at reflux temperature for a few minutes and then stirred at rt for 1 h. The reaction was quenched be the slow addition of water (5 ml) keeping the temperature below 50° C., then cooled with an ice bath and aqueous NaOH (4 M, 5 ml) was added. The reaction mixture was diluted with diethylether (200 ml) and extracted with 1 N aqueous hydrochloric acid. The aqueous layers were combined, basified with concentrated aqueous ammonia and extracted with diethylether. The organic layers were dried over sodium sulfate and the solvent was evaporated under reduced pressure to give the title compound as yellow oil (13.8 g, 77%). [1H-NMR (DMSO-d6, 600 MHz) δ 6.21 (s, 1H), 3.95 (q, 1H), 2.49-2.47 (m, 2H), 1.89 (br s, 2H), 1.25 (d, 3H), 0.90 (s, 9H]

Provenance & Evidence