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【结 构 式】

【分子编号】36280

【品名】(2S,5R)-5-([[tert-butyl(dimethyl)silyl]oxy]methyl)-3-fluoro-2,5-dihydro-2-furanol

【CA登记号】

【 分 子 式 】C11H21FO3Si

【 分 子 量 】248.3698432

【元素组成】C 53.2% H 8.52% F 7.65% O 19.33% Si 11.31%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(VIIb)

L-Glyceraldehyde acetonide (I) was subjected to Horner-Emmons reaction with triethyl alpha-fluorophosphonoacetate (II) in the presence of sodium bis(trimethylsilyl)amide to yield a mixture of Z (III) and E (IV) unsaturated esters. Acidic treatment of this mixture, followed by silylation with tert-butyldimethylsilyl chloride gave the desired fluorobutyrolactone (V) along with the open-chain silylated dihydroxyester (VI), which were separated by column chromatography. Reduction of lactone (V) with DIBAL provided an anomeric mixture of lactols (VIIa-b), which was further acetylated to afford (VIIIa-b). N-Glycosylation of the silylated N(4)-benzoylcytosine (IX) using trimethylsilyl triflate gave rise to the mixture of furanosylcytosines (Xa-b). After chromatographic isolation of the desired beta-anomer, deprotection of the silyl ether by means of tetrabutylammonium fluoride yielded (XI). Finally, ammonolysis of the N-benzoyl group of (XI) furnished the title compound.

1 Schinazi, R.F.; Choi, Y.; Chu, C.K.; Gullen, E.; Lee, K.; Schlueter-Wirtz, S.; Cheng, Y.-C.; Synthesis and anti-HIV and anti-HBV activities of 2'-fluoro-2',3'-unsaturated L-nucleosides. J Med Chem 1999, 42, 7, 1320.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(VIIa) 36279 (2R,5R)-5-([[tert-butyl(dimethyl)silyl]oxy]methyl)-3-fluoro-2,5-dihydro-2-furanol C11H21FO3Si 详情 详情
(VIIb) 36280 (2S,5R)-5-([[tert-butyl(dimethyl)silyl]oxy]methyl)-3-fluoro-2,5-dihydro-2-furanol C11H21FO3Si 详情 详情
(VIIIa) 36281 (2S,5R)-5-([[tert-butyl(dimethyl)silyl]oxy]methyl)-3-fluoro-2,5-dihydro-2-furanyl acetate C13H23FO4Si 详情 详情
(VIIIb) 36282 (2R,5R)-5-([[tert-butyl(dimethyl)silyl]oxy]methyl)-3-fluoro-2,5-dihydro-2-furanyl acetate C13H23FO4Si 详情 详情
(Xa) 36284 N-[1-[(2R,5R)-5-([[tert-butyl(dimethyl)silyl]oxy]methyl)-3-fluoro-2,5-dihydro-2-furanyl]-5-fluoro-2-oxo-1,2-dihydro-4-pyrimidinyl]benzamide C22H27F2N3O4Si 详情 详情
(Xb) 36285 N-[1-[(2S,5R)-5-([[tert-butyl(dimethyl)silyl]oxy]methyl)-3-fluoro-2,5-dihydro-2-furanyl]-5-fluoro-2-oxo-1,2-dihydro-4-pyrimidinyl]benzamide C22H27F2N3O4Si 详情 详情
(I) 14969 (4S)-2,2-dimethyl-1,3-dioxolane-4-carbaldehyde 22323-80-4 C6H10O3 详情 详情
(II) 18192 ethyl 2-(diethoxyphosphoryl)-2-fluoroacetate 2356-16-3 C8H16FO5P 详情 详情
(III) 36276 ethyl (E)-3-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-2-fluoro-2-propenoate C10H15FO4 详情 详情
(IV) 36287 ethyl (Z)-3-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-2-fluoro-2-propenoate C10H15FO4 详情 详情
(V) 36277 (5R)-5-([[tert-butyl(dimethyl)silyl]oxy]methyl)-3-fluoro-2(5H)-furanone C11H19FO3Si 详情 详情
(VI) 36278 ethyl (Z,4R)-4,5-bis[[tert-butyl(dimethyl)silyl]oxy]-2-fluoro-2-pentenoate C19H39FO4Si2 详情 详情
(IX) 36283 N-(5-fluoro-2-oxo-1,2-dihydro-4-pyrimidinyl)benzamide C11H8FN3O2 详情 详情
(XI) 36286 N-[5-fluoro-1-[(2S,5R)-3-fluoro-5-(hydroxymethyl)-2,5-dihydro-2-furanyl]-2-oxo-1,2-dihydro-4-pyrimidinyl]benzamide C16H13F2N3O4 详情 详情
Extended Information