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【结 构 式】

【分子编号】69299

【品名】(1S,2S,4S)-1-benzyl 2-methyl 4-hydroxycyclopentane-1,2-dicarboxylate

【CA登记号】 

【 分 子 式 】C15H18O5

【 分 子 量 】278.30492

【元素组成】C 64.74% H 6.52% O 28.74%

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:(XVIII)

Esterification of 1,2,3,4-butanetetracarboxylic acid (XXXVI) with EtOH in the presence of H2SO4 in refluxing toluene yields the corresponding tetraethyl ester (XXXVII), which upon treatment with NaOMe in MeOH followed by HCl in refluxing H2O yields trans-4-oxocyclopentane-1,2-dicarboxylic acid (rac-[XXXVIII]). Reduction of intermediate (XXXVIII) with H2 over Rh/C in the presence of NaOH in H2O followed by treatment with H2SO4 in acetone furnishes meso-4-hydroxycyclopentane-1,2-dicarboxylic acid (rac-[XXXIX]), which upon treatment with ethyl chloroformate in the presence of Et3N in THF affords lactone acid (rac-[VI]). Acid rac-(VI) is esterified with benzyl alcohol in the presence of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) and DMAP in EtOAc. Benzyl ester (rac-[XL]) is treated with Amberlyst-15 or MsOH in MeOH, affording racemic cyclopentanol (rac-[XVIII]). Finally, racemate rac-(XVIII) is resolved by chiral HPLC, yielding the desired (R,R,R)-isomer intermediate (XVIII) .
Intermediate (XV) is prepared from intermediate (XVIII) by hydrogenolysis with H2 over Pd/C in THF or DMF and subsequent amidation of the resulting carboxylic acid (XLI) with N-methylhex-5-enamine (VII) in the presence of DIEA, HATU or O-(benzotriazol-1-yl)-N,N,N’,N’-tetramethyluronium hexafluorophosphate (HBTU) in DMF or acetonitrile, or EDC in the presence or absence of DMAP in THF or CH2Cl2, or EEDQ in refluxing THF .

1 Llinas-Brunet, M., Bailey, M.D., Cameron, D. et al. (Boehringer Ingelheim [Canada] Ltd.). Hepatitis C inhibitor tri-peptides. CA 2338946, EP 1105413, EP 2028186, JP 2002522554, US 6323180, WO 2000009543.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
rac-(VI) 69297 racemic 3-oxo-2-oxabicyclo[2.2.1]heptane-5-carboxylic acid   C7H8O4 详情 详情
rac-(XL) 69300 racemic benzyl 3-oxo-2-oxabicyclo[2.2.1]heptane-5-carboxylate   C14H14O4 详情 详情
rac-(XVIII) 69298 racemic 1-benzyl 2-methyl 4-hydroxycyclopentane-1,2-dicarboxylate   C15H18O5 详情 详情
(VII) 69268 N-methylhex-5-enamine;N-methylhex-5-en-1-amine   C7H15N 详情 详情
(XV) 69276 (1S,2S,4S)-methyl 2-(hex-5-en-1-yl(methyl)carbamoyl)-4-hydroxycyclopentanecarboxylate   C15H25NO4 详情 详情
(XVIII) 69299 (1S,2S,4S)-1-benzyl 2-methyl 4-hydroxycyclopentane-1,2-dicarboxylate   C15H18O5 详情 详情
(XXXVI) 56634 1,2,3,4-butanetetracarboxylic acid;1,2,3,4-Tetracarboxybutane 1703-58-8 C8H10O8 详情 详情
(XXXVII) 69294 tetraethyl butane-1,2,3,4-tetracarboxylate   C16H26O8 详情 详情
(XXXVIII) 69295 racemic 4-oxocyclopentane-1,2-dicarboxylic acid   C7H8O5 详情 详情
(XXXIX) 69296 racemic 4-hydroxycyclopentane-1,2-dicarboxylic acid   C7H10O5 详情 详情
(XLI) 69301 (1S,2S,4S)-4-hydroxy-2-(methoxycarbonyl)cyclopentanecarboxylic acid   C8H12O5 详情 详情
Extended Information