Trifluoroacetic acid → alpha-(R)-(3-(S)-((4-(6-ethoxy-benzo[d]isoxazol-3-yl)piperidin-1-yl)methyl)-4-(S)-phenylpyrrolidin-1-yl)-cyclohexaneacetic acid

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Reaction Steps

A solution of 1-(4-((2,4-difluorophenyl)-hydroxyimino-methyl)piperidin-1-yl)ethanone (from Step A) and KOH (45 wt. % solution) in EtOH was refluxed for 24 hours. The products were coupled with of α-(R)-(3-(R)-formyl-4-(S)-phenylpyrrolidin-1-yl)-cyclohexaneacetic acid, 4-methoxybenzyl ester (prepared above as Aldehyde 5) using a procedure analogous to that described in Example 89, Step C. The products were treated with TFA and anisole for 18 hours and concentrated under reduced pressure. The residue was purified by prep HPLC (Zorbax-RX C8 column, 30% CH3CN 15 min. and 100% CH3CN, 20 mL/min., 254 nm) to provide α-(R)-(3-(S)-((4-(6-ethoxy-benzo[d]isoxazol-3-yl)piperidin-1-yl)methyl)-4-(S)-phenylpyrrolidin-1-yl)-cyclohexaneacetic acid: ESI-MS 546 (M+1); HPLC A: 3.01 min.; and α-(R)-(3-(S)-((4-(6-fluoro-benzo[d]isoxazol-3-yl)piperidin-1-yl)methyl)-4-(S)-phenylpyrrolidin-1-yl)-cyclohexaneacetic acid: ESI-MS 520 (M+1); HPLC A: 2.88 min.

Provenance & Evidence