Sodium Hydroxide → HCID 42635307, compound

Participants

Reaction Conditions

Reaction Steps

The resulting benzoic acid (S)-pyrrolidin-3-yl ester hydrochloride (0.45 mmol), (2R,4S)-4-[(3,5-bis-trifluoromethyl-benzyl)-(5-bromo-pyrimidin-2-yl)-amino]-2-ethyl-pyrrolidine-1-carboxylic acid isopropyl ester (0.196 mmol; 114 mg), tris(dibenzylideneacetone)dipalladium(0) (0.0098 mmol; 9.0 mg), 2-(di-tert-butylphosphino)biphenyl (0.0196 mmol; 5.8 mg) and sodium tert-butoxide (0.784 mmol; 75.3 mg) are dissolved in toluene (1 mL). The mixture is stirred for 2.5 hours at 100° C. To the mixture are added aqueous 1 M NaOH (5 mL), MeOH (10 mL) and THF (3 mL) at room temperature. After stirring for 5 hours, 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-((S)-3-hydroxy-pyrrolidin-1-yl)-pyrimidin-2-yl]-amino}-2-ethyl-pyrrolidine-1-carboxylic acid isopropyl ester (82 mg, 71%); ESI-MS m/z: 590 [M+1]+, Retention time 2.15 min (condition A).

Provenance & Evidence