Sodium Hydroxide → N,beta,beta-trimethyl-L-phenylalanyl-N1-{(1S,2E)-1-isopropyl-4-[methoxy(methyl)-amino]-3-methyl-4-oxobut-2-enyl}-N1,3-dimethyl-L-valinamide

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A solution of N,β,β-trimethyl-L-phenylalanyl-N1-[(1S,2E)-3-carboxy-1-isopropylbut-2-enyl]-N1,3-dimethyl-L-valinamide (473 mg, 1 mmol, WO 99/32509) in tetrahydrofuran (2 mL) is added a solution of N,O-dimethylhydroxylamine hydrochloride (166 mg, 1.7 mmol) in water (2 mL), adjusting the reaction mixture to pH 4.5 by adding dropwise 1.0 N sodium hydroxide solution. To this is added dropwise a solution of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimine hydrochloride (479 mg, 2.5 mmol) in water (7 mL) over a period of 7 min, maintaining pH 4.5 by using 1.0 N sodium hydroxide solution. The reaction mixture is stirred at room temperature for 2.5 h, adjusting the pH to 6-7. To this is added brine (10 mL) and extracted with dichloromethane. The combined organic layers are washed with brine, dried (Na2SO4), filtered and concentrated to give 491 mg (95%) of the title compound as a white solid. HRMS (ESI) calcd for C29H48N4O4 (M+H+) 517.3748, found 517.3750.

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