methyl (1R,2R)-2-[(3'-fluoro-4'-{[6-(trifluoromethoxy)-1,3-benzothiazol-2-yl]amino}-1,1'-biphenyl-4-yl)carbonyl]cyclopentanecarboxylate → (1R,2R)-2-{[4-(3-fluoro-4-{[6-(trifluoromethoxy)-1,3-benzothiazol-2-yl]amino}phenyl)phenyl]carbonyl}cyclopentane-1-carboxylic acid

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Reaction Steps

In 250-mL round-bottom flask, methyl (1R,2R)-2-[(3′-fluoro-4′-{[6-(trifluoromethoxy)-1,3-benzothiazol-2-yl]amino}-1,1′-biphenyl-4-yl)carbonyl]cyclopentanecarboxylate (2.53 g, 4.53 mmol) was dissolved in 100 mL of 1:1 THF/dioxane containing 5.0 molar equivalents of 1 N aqueous NaOH. The mixture was stirred at rt overnight. The mixture was concentrated under reduced pressure to a volume of about 20 mL. Ethyl acetate (100 mL), water (30 mL), and 5.1 molar equivalents of 1 N aqueous HCl were added to the mixture. The mixture was transferred to a separation funnel. The organic layer was washed with water (1×50 mL), dried (Na2SO4), and concentrated under reduced pressure. The solid was ultrasonicated in 30 mL acetonitrile and filtered to give the desired compound as a white solid (1.96 g, 80%, 94.5% ee). 1H NMR (400 MHz, DMSO-d6) δ 12.20 (br s, 1H), 10.60 (bs, 1H), 8.70 (t, 1H), 7.60-8.20 (m, 8H), 7.30 (d, 1H), 4.70 (q, 1H), 3.20 (q, 1H), 2.20 (m, 1H), 2.00 (m, 1H), 1.50-1.90 (m, 4H); LC-MS m/z 545.3 (MH+), ret. time 3.93 min.

Provenance & Evidence