[Synthesis]
Calcium salt of (3R,5R)-7-[2-(4-fluorophenyl)-5-isopropyl-3-phenyl-4-(phenylcarbamoyl)-1H-pyrrol-1-yl]-3,5-dihydroxyheptanoic acid (500 mg, 0.413 mmol) was used as a raw material, which was suspended in water (8 mL), EtOAc (4 mL) was added, and the mixture was cooled in an ice bath (4°C). An aqueous 0.2 M HCl solution (4.55 mL, 0.910 mmol) was added slowly and dropwise under vigorous stirring until a clarified solution was formed. The reaction mixture was gradually warmed to room temperature, followed by separation of the organic and aqueous layers. The aqueous layer was extracted with EtOAc (3 x 5 mL), the combined organic layers were washed with brine (5 mL), dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The resulting foam (469 mg) was dissolved in toluene (20 mL) and the mixture was heated to 0°C and refluxed for 2.5 h under a Dean-Stark apparatus. Upon completion of the reaction, the mixture was cooled to room temperature and concentrated under reduced pressure. Purification by fast column chromatography (eluent: heptane/EtOAc, gradient from 1:3 to 1:5) afforded the target product 5-(4-fluorophenyl)-2-(1-methylethyl)-N,4-diphenyl-1-[2-[(2R,4R)-tetrahydro-4-hydroxy-6-oxo-2H-pyran-2-yl]ethyl]-1H-pyrrole-3-carboxamide (394 mg. (white foamy substance). NMR hydrogen spectrum (400 MHz, CDCl3) δ 7.24-7.10 (m, 9H), 7.09-6.96 (m, 5H), 6.92-6.82 (br s, 1H), 4.57-4.47 (m, 1H), 4.34-4.27 (m, 1H), 4.27-4.16 (m, 1H), 4.09-3.97 (m , 1H), 3.62-3.47 (m, 1H), 2.66 (ABdd, J = 17.7, 4.8 Hz, 1H), 2.55 (ABddd, J = 17.7, 3.4, 1.5 Hz, 1H), 2.11 (d, J = 2.9 Hz, 1H), 1.95-1.82 (m, 1H), 1.81-1.67 (m, 2H) , 1.63-1.57 (m, 1H), 1.56-1.45 (m, 6H). |