【结 构 式】 |
【分子编号】27913 【品名】(2S)-1,1,2-triphenyl-1,2-ethanediol 【CA登记号】95061-46-4 |
【 分 子 式 】C20H18O2 【 分 子 量 】290.36172 【元素组成】C 82.73% H 6.25% O 11.02% |
合成路线1
该中间体在本合成路线中的序号:(IV)The synthesis of atorvastatin [14C]-labeled on the side chain has been described: The reaction of [14C]-labeled sodium acetate (I) with phthaloyl chloride (II) in refluxing xylene gives the acyl chloride (III), which is treated with 1,2,2-triphenyl-1(S),2-ethanediol (IV) in dichloromethane yielding the expected monoacetate (V). The condensation of (V) with the pyrrolepropionaldehyde (VI) by means of lithium diisopropylamide (LDA) in THF affords the chiral beta-hydroxyester (VII), which is transesterified with sodium methoxide in methanol providing the corresponding methyl ester (VIII). The condensation of (VIII) with tert-butyl acetate (IX) by means of LDA in THF gives the beta-oxo-delta-hydroxyester (X), which is regioselectively reduced to the dihydroxyester (XI) by means of BEt3, NaBH4 and H2O2 in THF. The hydrolysis of (XI) with NaOH in THF/water, followed by acidification yields the free acid (XII), which is heated in refluxing toluene in a Dean-Stark trap to provide lactone (XIII). The reaction of (XIII) with NaOH in THF/methanol gives the corresponding sodium salt (XIV), which is finally treated with CaCl2 in the same solvent.
【1】 Woo, P.W.K.; Lee, H.T.; Atorvastatin, an HMG-CoA reductase inhibitor and effective lipid-regulating agent. Part II. Synthesis of side-chain-labeled [C-14] atorvastatin. J Label Compd Radiopharm 1999, 42, 2, 129. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(I) | 27912 | Sodium acetate | 127-09-3 | C2H3NaO2 | 详情 | 详情 |
(I) | 45240 | sodium acetate | C2H3NaO2 | 详情 | 详情 | |
(II) | 23811 | phthaloyl dichloride;1,2-Benzenedicarbonyl dichloride;o-Phthaloyl chloride | 88-95-9 | C8H4Cl2O2 | 详情 | 详情 |
(III) | 19273 | acetyl chloride | 75-36-5 | C2H3ClO | 详情 | 详情 |
(III) | 45241 | acetyl chloride | C2H3ClO | 详情 | 详情 | |
(IV) | 27913 | (2S)-1,1,2-triphenyl-1,2-ethanediol | 95061-46-4 | C20H18O2 | 详情 | 详情 |
(V) | 11540 | (1S)-2-hydroxy-1,2,2-triphenylethyl acetate; (R)-(+)-1,1,2-Triphenyl-1,2-ethanediol 2-acetate | 95061-47-5 | C22H20O3 | 详情 | 详情 |
(V) | 45242 | (1S)-2-hydroxy-1,2,2-triphenylethyl acetate | C22H20O3 | 详情 | 详情 | |
(VI) | 15386 | 5-(4-fluorophenyl)-2-isopropyl-1-(3-oxopropyl)-N,4-diphenyl-1H-pyrrole-3-carboxamide | C29H27FN2O2 | 详情 | 详情 | |
(VII) | 15395 | (1S)-2-hydroxy-1,2,2-triphenylethyl (3R)-5-[3-(anilinocarbonyl)-5-(4-fluorophenyl)-2-isopropyl-4-phenyl-1H-pyrrol-1-yl]-3-hydroxypentanoate | 134394-96-0 | C51H47FN2O5 | 详情 | 详情 |
(VII) | 45243 | (1S)-2-hydroxy-1,2,2-triphenylethyl (3R)-5-[3-(anilinocarbonyl)-5-(4-fluorophenyl)-2-isopropyl-4-phenyl-1H-pyrrol-1-yl]-3-hydroxypentanoate | C51H47FN2O5 | 详情 | 详情 | |
(VIII) | 15396 | methyl (3R)-5-[3-(anilinocarbonyl)-5-(4-fluorophenyl)-2-isopropyl-4-phenyl-1H-pyrrol-1-yl]-3-hydroxypentanoate | C32H33FN2O4 | 详情 | 详情 | |
(VIII) | 45244 | methyl (3R)-5-[3-(anilinocarbonyl)-5-(4-fluorophenyl)-2-isopropyl-4-phenyl-1H-pyrrol-1-yl]-3-hydroxypentanoate | C32H33FN2O4 | 详情 | 详情 | |
(IX) | 15397 | tert-butyl acetate | 540-88-5 | C6H12O2 | 详情 | 详情 |
(X) | 15398 | tert-butyl (5R)-7-[3-(anilinocarbonyl)-5-(4-fluorophenyl)-2-isopropyl-4-phenyl-1H-pyrrol-1-yl]-5-hydroxy-3-oxoheptanoate | C37H41FN2O5 | 详情 | 详情 | |
(X) | 45245 | tert-butyl (5R)-7-[3-(anilinocarbonyl)-5-(4-fluorophenyl)-2-isopropyl-4-phenyl-1H-pyrrol-1-yl]-5-hydroxy-3-oxoheptanoate | C37H41FN2O5 | 详情 | 详情 | |
(XI) | 27914 | tert-butyl (3R,5R)-7-[3-(anilinocarbonyl)-5-(4-fluorophenyl)-2-isopropyl-4-phenyl-1H-pyrrol-1-yl]-3,5-dihydroxyheptanoate | C37H43FN2O5 | 详情 | 详情 | |
(XI) | 45246 | tert-butyl (3R,5R)-7-[3-(anilinocarbonyl)-5-(4-fluorophenyl)-2-isopropyl-4-phenyl-1H-pyrrol-1-yl]-3,5-dihydroxyheptanoate | C37H43FN2O5 | 详情 | 详情 | |
(XII) | 15390 | (3R,5R)-7-[3-(anilinocarbonyl)-5-(4-fluorophenyl)-2-isopropyl-4-phenyl-1H-pyrrol-1-yl]-3,5-dihydroxyheptanoic acid | C33H35FN2O5 | 详情 | 详情 | |
(XII) | 45247 | (3R,5R)-7-[3-(anilinocarbonyl)-5-(4-fluorophenyl)-2-isopropyl-4-phenyl-1H-pyrrol-1-yl]-3,5-dihydroxyheptanoic acid | C33H35FN2O5 | 详情 | 详情 | |
(XIII) | 15391 | 5-(4-fluorophenyl)-1-[2-[(2R,4R)-4-hydroxy-6-oxotetrahydro-2H-pyran-2-yl]ethyl]-2-isopropyl-N,4-diphenyl-1H-pyrrole-3-carboxamide | C33H33FN2O4 | 详情 | 详情 | |
(XIII) | 45248 | 5-(4-fluorophenyl)-1-[2-[(2R,4R)-4-hydroxy-6-oxotetrahydro-2H-pyran-2-yl]ethyl]-2-isopropyl-N,4-diphenyl-1H-pyrrole-3-carboxamide | C33H33FN2O4 | 详情 | 详情 | |
(XIV) | 27911 | sodium (3R,5R)-7-[3-(anilinocarbonyl)-5-(4-fluorophenyl)-2-isopropyl-4-phenyl-1H-pyrrol-1-yl]-3,5-dihydroxyheptanoate | C33H34FN2NaO5 | 详情 | 详情 | |
(XIV) | 45249 | sodium (3R,5R)-7-[3-(anilinocarbonyl)-5-(4-fluorophenyl)-2-isopropyl-4-phenyl-1H-pyrrol-1-yl]-3,5-dihydroxyheptanoate | C33H34FN2NaO5 | 详情 | 详情 |