Morpholine → (2R,4S)-4-[(3,5-Bis-trifluoromethyl-benzyl)-(5-morpholin-4-yl-pyrimidin-2-yl)-amino]-2-ethyl-pyrrolidine-1-carboxylic acid tert-butyl ester

Participants

Reaction Conditions

Reaction Steps

(2R,4S)-4-[(3,5-Bis-trifluoromethyl-benzyl)-(5-bromo-pyrimidin-2-yl)-amino]-2-ethyl-pyrrolidine-1-carboxylic acid tert-butyl ester (0.50 mmol; 299 mg), morpholine (1.0 mmol; 87 mg), tris(dibenzylideneacetone)dipalladium(0) (0.025 mmol; 22.9 mg), 2-(di-tert-butylphosphino)biphenyl (0.05 mmol; 14.9 mg) and sodium tert-butoxide (1.0 mmol; 96 mg) are dissolved in toluene (2.5 mL). The mixture is stirred for 3 hours at 100° C., and then cooled to ambient temperature. The reaction mixture is quenched with saturated aqueous ammonium chloride solution. The product is extracted three times with EtOAc. The combined organic layer is washed with brine, dried over Na2SO4, filtered, concentrated under reduced pressure. The obtained residue is purified by silica gel column chromatography (eluent: n-hexane/EtOAc) to give (2R,4S)-4-[(3,5-Bis-trifluoromethyl-benzyl)-(5-morpholin-4-yl-pyrimidin-2-yl)-amino]-2-ethyl-pyrrolidine-1-carboxylic acid tert-butyl ester (247 mg, 82%); ESI-MS m/z: 604 [M+1]+, Retention time 4.91 min (condition C).

Provenance & Evidence