Sodium Hydroxide → (2-(((4-(1,3-Dihydro-1-oxo-2H-isoindol-2-yl)butyl)hydroxyphosphinyl)methyl)-4-phenylbutanoyl)-L-leucine N-phenylamide

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Reaction Steps

(2-(((4-(1,3-Dihydro-1-oxo-2H-isoindol-2-yl)butyl)methoxyphosphinyl)methyl)-4-phenylbutanoyl)-L-leucine N-phenylamide (0.31 g, 0.49 mmol) from Step C was dissolved in methanol (10 mL). The solution was cooled in an ice bath and 2N aqueous sodium hydroxide (5 mL, 10 mmol) was added. The solution was allowed to warm to room temperature and was stirred for an additional 12 h before being diluted with 2N aqueous hydrochloric acid (40 mL) and extracted with ethyl acetate (75 mL). The organic extract was washed with saturated aqueous sodium chloride (25 mL), dried (sodium sulfate), and evaporated. The crude product was purified by high pressure liquid chromatography on a.22 mm×25 cm reverse phase column (Whatman ODS-3, Partisil 10) eluting with 45% acetonitrile/55% water/0.05% trifluoroacetic acid (flow rate of 20 mL/min, detection at 250 nm). Evaporation of appropriate fractions gave 264 mg the desired product (88% yield) as a colorless brittle foam.

Provenance & Evidence