1-(1,4-dioxaspiro[4.5]dec-7-ylmethyl)-4-phenyl-1,2,3,6-tetrahydropyridine -Drug Synthesis Database

【结构式】

【分子编号】54938

【品名】1-(1,4-dioxaspiro[4.5]dec-7-ylmethyl)-4-phenyl-1,2,3,6-tetrahydropyridine

【CA登记号】

【分子式】C₂₀H₂₇NO₂

【分子量】313.43992

【元素组成】C 76.64% H 8.68% N 4.47% O 10.21%

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：(VII)

Ethyl 3-oxocyclohexanecarboxylate (I) was protected as the ethylene ketal (II) and its ethyl ester group was subsequently hydrolyzed to carboxylic acid (III). After activation of acid (III) as the mixed anhydride (IV) with isobutyl chloroformate, coupling with 4-phenyl-1,2,3,6-tetrahydropyridine (V) gave amide (VI). Reduction of amide (VI) to the corresponding amine (VII) was accomplished by treatment with LiAlH4 in the presence of AlCl3. Addition of phenylmagnesium bromide to the ketone (VIII), obtained by acidic hydrolysis of ketal (VII), provided the tertiary alcohol (IX). Dehydration of alcohol (IX) by means of trifluoroacetic acid gave rise to a mixture of isomeric cyclohexene derivatives (X) and (XI), which were separated by column chromatography. The racemic 3-cyclohexenyl isomer (XI) was then resolved via formation of the salts with (R)-1,1'-binaphthyl-2,2'-diyl hydrogen phosphate to furnish the title (R)-(+)-enantiomer.

参考文献中间体

合成目标

【1】 Caprathe, B.W.; Downing, D.M.; Jaen, J.C.; Johnson, S.J.; Smith, W.J. III; Wise, L.D.; Wright, J.; Wustrow, D.J. (Pfizer Inc.); 1,3-Substd. cycloalkenes and cycloalkanes as central nervous system agents. EP 0545095; EP 0613465; JP 1995501075; US 5314896; WO 9310092 .

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)	54933	ethyl 3-oxocyclohexanecarboxylate		C₉H₁₄O₃	详情	详情
(II)	54934	ethyl 1,4-dioxaspiro[4.5]decane-7-carboxylate		C₁₁H₁₈O₄	详情	详情
(III)	54935	1,4-dioxaspiro[4.5]decane-7-carboxylic acid		C₉H₁₄O₄	详情	详情
(IV)	54936			C₁₄H₂₂O₆	详情	详情
(V)	13002	4-Phenyl-1,2,3,6-tetrahydropyridine; 1,2,3,6-Tetrahydro-4-phenyl-pyridine	10338-69-9	C₁₁H₁₃N	详情	详情
(VI)	54937	1,4-dioxaspiro[4.5]dec-7-yl[4-phenyl-3,6-dihydro-1(2H)-pyridinyl]methanone	n/a	C₂₀H₂₅NO₃	详情	详情
(VII)	54938	1-(1,4-dioxaspiro[4.5]dec-7-ylmethyl)-4-phenyl-1,2,3,6-tetrahydropyridine		C₂₀H₂₇NO₂	详情	详情
(VIII)	54939	3-{[4-phenyl-3,6-dihydro-1(2H)-pyridinyl]methyl}cyclohexanone		C₁₈H₂₃NO	详情	详情
(IX)	54940	1-phenyl-3-{[4-phenyl-3,6-dihydro-1(2H)-pyridinyl]methyl}cyclohexanol		C₂₄H₂₉NO	详情	详情
(X)	54941	4-phenyl-1-[(3-phenyl-2-cyclohexen-1-yl)methyl]-1,2,3,6-tetrahydropyridine		C₂₄H₂₇N	详情	详情
(XI)	54942	4-phenyl-1-[(3-phenyl-3-cyclohexen-1-yl)methyl]-1,2,3,6-tetrahydropyridine		C₂₄H₂₇N	详情	详情

Extended Information