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【结 构 式】

【分子编号】50002

【品名】3-Cyclopentenecarboxylic acid

【CA登记号】7686-77-3

【 分 子 式 】C6H7ClO

【 分 子 量 】130.57368

【元素组成】C 55.19% H 5.4% Cl 27.15% O 12.25%

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:(V)

The cyclization of diethyl malonate (I) with cis-1,4-dichloro-2-butene (II) by means of LiH in DMF gives 3-cyclopentene-1,1-dicarboxylic acid diethyl ester (III), which is monodecarboxylated by hydrolysis with NaOH in ethanol, followed by heating at 170-180 C to yield 3-cyclopentene-1-carboxylic acid (IV). The reaction of (IV) with SOCl2 affords the acyl chloride (V), which by reaction with ethanol provides the ethyl ester (VI). The oxidation of (VI) with OsO4 and N-methylmorpholine N-oxide (NMMO) in acetone/water gives the dihydroxy compound (VII), which is further oxidized with NaIO4 in THF to yield the dialdehyde (VIII). The cyclization of (VIII) by means of glycine ethyl ester and acetonedicarboxylic acid affords the 9-azabicyclo[3,3,1]nonan-3-one derivative (IX), which is reduced with NaBH4 in ethanol to provide the corresponding alcohol (X). The protection of the OH group of (X) with dihydropyran and methanesulfonic acid gives the tetrahydropyranyl ether (XI), which is cyclized by means of tBuO-K in hot toluene, yielding the tricyclic ketone (XII). The deprotection of (XII) with 5N HCl affords the alcohol (XIII), which is finally esterified with 1H-indole-3-carbonyl chloride (XIV) by means of tetrafluoroboric acid and silver tetrafluoroborate in nitroethane. Alternatively, 1H-indole (XV) is condensed with oxalyl chloride (XVI) to give 3-indolylglyoxylyl chloride (XVII), which is used to acylate the alcohol (XIII) by means of tetrafluoroboric acid and silver tetrafluoroborate as before. Simultaneous decarbonylation takes place in this acylation reaction.

1 Gittos, M.W. (Merrell Pharmaceuticals, Inc.); Esters of hexahydro-8-hydroxy-2, 6-methano-2H-quinolizin-3(4H)-one and related compds.. AU 8780596; EP 0266730; JP 1988258476 .
2 Gittos, M.W.; Fatmi, M.; Potent 5-HT3 antagonists incorporating a novel bridged pseudopelletierine ring system. Actual Chim Ther 1989, 16, 187.
3 Gittos, M.W.; Fatmi, M.; Galvan, M.; Dolasetron Mesylate. Drugs Fut 1993, 18, 6, 506.
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) 16829 Diethyl malonate 105-53-3 C7H12O4 详情 详情
(II) 50004 cis-1,4-Dichloro-2-butene;(Z)-1,4-Dichlorobutene;(Z)-1,4-Dichloro-2-butene;(2Z)-1,4-Dichloro-2-butene;cis-1,2-Bis(chloromethyl)ethene 1476-11-5 C4H6Cl2 详情 详情
(III) 50000 diethyl 3-cyclopentene-1,1-dicarboxylate C11H16O4 详情 详情
(IV) 50001 3-cyclopentene-1-carboxylic acid C6H8O2 详情 详情
(V) 50002 3-Cyclopentenecarboxylic acid 7686-77-3 C6H7ClO 详情 详情
(VI) 13469 ethyl 3-cyclopentene-1-carboxylate C8H12O2 详情 详情
(VII) 13470 ethyl 3,4-dihydroxycyclopentanecarboxylate C8H14O4 详情 详情
(VIII) 13471 ethyl 4-oxo-2-(2-oxoethyl)butanoate C8H12O4 详情 详情
(IX) 13472 ethyl 9-(2-ethoxy-2-oxoethyl)-7-oxo-9-azabicyclo[3.3.1]nonane-3-carboxylate C15H23NO5 详情 详情
(X) 13473 ethyl 9-(2-ethoxy-2-oxoethyl)-7-hydroxy-9-azabicyclo[3.3.1]nonane-3-carboxylate C15H25NO5 详情 详情
(XI) 13474 ethyl 9-(2-ethoxy-2-oxoethyl)-7-(tetrahydro-2H-pyran-2-yloxy)-9-azabicyclo[3.3.1]nonane-3-carboxylate C20H33NO6 详情 详情
(XII) 50003 5-(tetrahydro-2H-pyran-2-yloxy)-8-azatricyclo[5.3.1.0(3,8)]undecan-10-one C15H23NO3 详情 详情
(XIII) 13475 5-Hydroxy-8-azatricyclo[5.3.1.0(3,8)]undecan-10-one C10H15NO2 详情 详情
(XIV) 17153 1H-indole-3-carbonyl chloride C9H6ClNO 详情 详情
(XV) 15292 Indole; 1H-indole 120-72-9 C8H7N 详情 详情
(XVI) 29841 Oxalyl chloride; 2-Chloro-2-oxoacetyl chloride 79-37-8 C2Cl2O2 详情 详情
(XVII) 13476 Indole-3-glyoxylyl chloride; 2-(1H-Indol-3-yl)-2-oxoacetyl chloride 22980-09-2 C10H6ClNO2 详情 详情
Extended Information