HCID 14420372, compound → (4S)-4-[(tert-Butoxycarbonyl)amino]-5-ethoxy-5-oxopentanoic acid

Participants

Reaction Steps

To a mixture of (S)-2-tert-butoxycarbonylamino-pentanedioic acid 5-benzyl ester 1-ethyl ester (390 mg, 0.67 mmol; 63% purity) described in Manufacturing Example 4-1 and ethanol (4 mL) was added palladium-carbon (40 mg, 0.19 mmol; 50% water content) at room temperature, which was stirred overnight under a hydrogen atmosphere (1 atm) at room temperature. The reaction mixture was replaced with nitrogen and filtered through a Celite pad. The solvent was evaporated from the filtrate under a reduced pressure, so as to obtain (S)-2-tert-butoxycarbonylamino-pentanedioic acid 1-ethyl ester (330 mg) in a crude form. The crude product thus obtained was used directly in the next reaction. To a mixture of 3-(3-(4-(pyridin-2-yloxymethyl)-benzyl)-isoxazol-5-yl)-pyridin-2-ylamine (150 mg, 80.42 mmol) described in Reference Example 1 and acetonitrile (3 mL) were added (S)-2-tert-butoxycarbonylamino-pentanedioic acid 1-ethyl ester (crude, 230 mg), N-methylmorpholine (46 μL, 0.42 mmol), and 180 mg (0.46 mmol) of 047-azabenzotriazol-1-yl)-1,1,3,3-tetramethyl-uronium hexafluorophosphate (180 mg, 0.46 mmol) were added in this order at 0° C., which was stirred overnight at room temperature. Water was added to the reaction mixture, which was extracted with ethyl acetate. The organic layer was washed with saturated brine, and the solvent was evaporated under a reduced pressure. The residue was purified by NH silica gel column chromatography (ethyl acetate:heptane=4:1), so as to obtain the titled compound (47 mg).

Provenance & Evidence