CP-195543

(3S,4R)-7-(2-羧基-5-三氟甲基苯基)-4-羟基-3-苄基-3,4-二氢-2H-1-苯并吡喃Chemical Name: (+)-(3S,4R)-2-[3-Benzyl-4-hydroxy-3,4-dihydro-2H-benzopyran-7-yl]-4-(trifluoromethyl)benzoic acid
CAS No. 204981-48-6, 205990-47-2 (trans-isomer), 179107-34-7 (undefined stereoch.)
项目整合开发状态: Preclinical
项目研究机构: Pfizer (Originator)
合成路线:The reaction of 4(R)-benzyloxazolidin-2-one (I) with 3-phenylpropionyl chloride (II) by means of BuLi in THF gives 4(R)-benzyl-3-(3-phenylpropionyl)oxazolidin-2-one (III),which is condensed with 4-bromo-2-fluorobenzaldehyde (IV) by means of dibutylboron triflate or TiCl4 yielding the chiral intermediate (V).The reductive elimination of the oxazolidinone group affords (1R,2S)-2-benzyl-1-(4-bromo-2-fluorophenyl)propane-1,3-diol (VI),which is cyclized by means of sodium bis(trimethylsilyl)amide in hot DMSO to give the chiral dihydro-1-benzopyran (VII).The reaction of (VII) with the borane-THF complex and methyllithium in THF affords the boronic acid (VIII),which is condensed with 2-iodo-4-(trifluoromethyl)benzoic acid ethyl ester (IX) by means of KF and Pd/C in refluxing ethanol to provide the ethyl ester (X) of the target comopound.Finally,this compound is hydrolyzed with NaOH in refluxing isopropanol.