Methanol → 2-(3-ethoxy-4-propan-2-yloxyphenyl)-2-[4-(N-phenylmethoxycarbonylcarbamimidoyl)anilino]acetic acid

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Reaction Steps

To 141E (4.64 g, 8.9 mmol) in THF (20 mL) was added lithium hydroxide (17.8 mL, 1M, 17.8 mmol) then methanol (5 mL). After stirring for 2 h at rt, the reaction was concentrated and redissolved in ethyl acetate. The aqueous layer was neutralized and acidified to pH 3-4 using 10% citric acid. The product was extracted with ethyl acetate (3×) and washed with brine and dried over sodium sulfate. The solvent was removed to give 3.6 g of 2-(4-(N-(benzyloxycarbonyl)carbamimidoyl)phenylamino)-2-(3-ethoxy-4-isopropoxyphenyl)acetic acid as a yellow solid (80% yield). LC-MS: 506.11 (M+H)+. The enantiomers were separated using a semi-preparative HPLC equipped with an Astex Chirobiotic T column (20 mm×500 mm). The separation was performed using an isocratic method of methanol with 0.1% triethylamine plus 0.2% acetic acid to provide 141F.

Provenance & Evidence