Lithium Hydroxide → HCID 131729425, compound

Participants

Reaction Steps

Lithium hydroxide (444 mg, 10.8 mmol) was added to an ambient temperature solution of methyl 2-(acetylamino)-3-(4-{3-[(tert-butoxycarbonyl)amino]-1-methyl-1H-pyrazo 1-4-yl}phenyl)propanoate (450 mg, 1.08 mmol) in tetrahydrofuran/water (10:1) (11 mL). After stirring at ambient temperature for 1 h, the reaction mixture was diluted with water and extracted with ethyl acetate. The aqueous phase was acidified with 1.5 N hydrochloric acid and extracted with ethyl acetate. The combined organic extracts were dried (magnesium sulfate) and concentrated in vacuo. Sodium bicarbonate (727 mg, 8.66 mmol) was added to an ambient temperature solution of the crude residue, 1-amino-4,4-dimethylhexan-2-ol (314 mg, 2.16 mmol), 1-[3-(dimethylamino) propyl]-3-ethylcarbodiimide hydrochloride (415 mg, 2.16 mmol) and 1-hydroxybenzotriazole (292 mg, 2.16 mmol) in methylene chloride (20 mL). After stirring at ambient temperature overnight, the reaction was quenched with water and extracted with methylene chloride and ethyl acetate. The combined organic extracts were dried (magnesium sulfate) and concentrated in vacuo. Chromatography over silica eluting with 0-100% ethyl acetate/hexane afforded tert-butyl[4-(4-{2-(acetylamino)-3-[(2-hydroxy-4,4-dimethylhexyl)amino]-3-oxopropyl}phenyl)-1-methyl-1H-pyrazol-3-yl]carbamate.

Provenance & Evidence