methyl 4-butyl-2-cyclohexene-1-carboxylate -Drug Synthesis Database

【结构式】

【分子编号】54205

【品名】methyl 4-butyl-2-cyclohexene-1-carboxylate

【CA登记号】n/a

【分子式】C₁₂H₂₀O₂

【分子量】196.2896

【元素组成】C 73.43% H 10.27% O 16.3%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(IV)

The Birch reduction of 4-butylbenzoic acid (I) with Li in dry ammonia gives 4-butyl-3,4-dihydrobenzoic acid (II), which is submitted to a new Birch reduction to yield 4-butyl-2-cyclohexenecarboxylic acid (III). The methylation of (III) with methanol in acidic medium or with diazomethane, affords the corresponding methyl ester (IV), which is reduced with H2 over PtO2 in ethyl acetate to provide 4-butylcyclohexanecarboxylic acid methyl ester (V). This compound is hydrolyzed with NaOMe in methanol to give the expected carboxylic acid (VI) as a cis/trans mixture. This mixture is dissolved in a minimum amount of methanol, then thiourea and methanol are added and heated until a homogeneous mixture is obtained. The solution is allowed to cool and finally cools at -20 C; the resulting crystalline inclusion complex is filtered and decomposed with aq. KOH to yield trans-4-butylcyclohexanecarboxylic acid (VII). This compound is treated with SOCl2 in benzene to give the corresponding acyl chloride (VIII), which is finally condensed with testosterone (IX) by means of pyridine in benzene to provide the target testosterone ester. Alternatively, the intermediate trans-4-butylcyclohexanecarboxylic acid (VII) can also be obtained as follows: The reduction of 4-butylbenzoic acid (I) with H2 over PtO2 in acetic acid gives 4-butylcyclohexanecarboxylic acid (X) predominantly as the cis-isomer, which is treated with SOCl2 in dichloromethane to yield the acyl chloride (XI). The reaction of (XI) with anhydrous ethanol affords the ethyl ester (XII), which is submitted to a cis/trans isomerization with sodium ethoxide in refluxing ethanol to provide the target intermediate (VII).

参考文献中间体

合成目标

【1】 Acosta, C.K.; et al.; Tritium labeled trans-4-N-butyl-2,3-3H-cyclohexanecarboxylic acid. Preparation of testosterone 17beta-trans-4-N-butyl-2,3-3H-cyclohexanecarboxylate and [4-14C]-testosterone 17beta-trans-4-N-butylcyclohexane carboxylate. J Label Compd Radiopharm 1990, 28, 10, 1201.
【2】 Kim, H.K.; Blye, R.P.; Bialy, G.; Archer, S.; Fried, J.; Crabbe, P.; Djerassi, C.; Diczfalusy, E.R.; Long-acting androgenic cpds. and pharmaceutical compsns. thereof. US 4948790 .
【3】 Leysen, D.; Van der Louw, J.; Van der Voort, H.A.A. (Akzo Nobel N.V.); Cycloalkyl-carboxylic acid esters of 7alpha methyl-estr-4-en-3-one 17beta-ol (19-nor 7alpha-methyltestosterone). WO 9967270 .

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)	54202	4-Butylbenzoic acid; 4-n-Butylbenzoic acid	20651-71-2	C₁₁H₁₄O₂	详情	详情
(II)	54203	4-butyl-1,5-cyclohexadiene-1-carboxylic acid	n/a	C₁₁H₁₆O₂	详情	详情
(III)	54204	4-butyl-2-cyclohexene-1-carboxylic acid	n/a	C₁₁H₁₈O₂	详情	详情
(IV)	54205	methyl 4-butyl-2-cyclohexene-1-carboxylate	n/a	C₁₂H₂₀O₂	详情	详情
(V)	54206	methyl 4-butylcyclohexanecarboxylate	n/a	C₁₂H₂₂O₂	详情	详情
(VI)	54207	4-butylcyclohexanecarboxylic acid	n/a	C₁₁H₂₀O₂	详情	详情
(VII)	54208	trans-4-n-Butylcyclohexanecarboxylic acid	38289-28-0	C₁₁H₂₀O₂	详情	详情
(VIII)	54209	4-butylcyclohexanecarbonyl chloride	n/a	C₁₁H₁₉ClO	详情	详情
(IX)	54210	17beta-Hydroxyandrost-4-en-3-one; 4-Androsten-17-beta-ol-3-one; Android; Androlin; delta4-Androsten-17beta-ol-3-one; Halotensin; Oreton; Testex; Testoderm; Testosterone; Testred; Virilon	58-22-0	C₁₉H₂₈O₂	详情	详情
(X)	54211	4-butylcyclohexanecarboxylic acid	38289-28-0	C₁₁H₂₀O₂	详情	详情
(XI)	54212	4-butylcyclohexanecarbonyl chloride	n/a	C₁₁H₁₉ClO	详情	详情
(XII)	54213	ethyl 4-butylcyclohexanecarboxylate	n/a	C₁₃H₂₄O₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IV)

The Birch reduction of 4-butylbenzoic acid (I) with Li in dry ammonia gives 4-butyl-3,4-dihydrobenzoic acid (II), which is submitted to a new Birch reduction to yield 4-butyl-2-cyclohexenecarboxylic acid (III). The methylation of (III) with methanol in acidic medium or with diazomethane, affords the corresponding methyl ester (IV), which is reduced with 3H2 over PtO2 in ethyl acetate to provide tritium-labeled 4-butylcyclohexanecarboxylic acid methyl ester (V). This compound is hydrolyzed with NaOMe in methanol to give the expected carboxylic acid (VI) as a cis/trans mixture. This mixture is dissolved in a minimum amount of methanol, then thiourea and methanol are added and heated until a homogeneous mixture is obtained. The solution is allowed to cool and finally cools at -20 C; the resulting crystalline inclusion complex is filtered and decomposed with aq. KOH to yield tritium-labeled trans-4-butylcyclohexanecarboxylic acid (VII) (1). This compound is treated with SOCl2 in benzene to give the corresponding acyl chloride (VIII), which is finally condensed with testosterone (IX) by means of pyridine in benzene to provide the target labeled testosterone ester.

参考文献中间体

合成目标

【1】 Acosta, C.K.; et al.; Tritium labeled trans-4-N-butyl-2,3-3H-cyclohexanecarboxylic acid. Preparation of testosterone 17beta-trans-4-N-butyl-2,3-3H-cyclohexanecarboxylate and [4-14C]-testosterone 17beta-trans-4-N-butylcyclohexane carboxylate. J Label Compd Radiopharm 1990, 28, 10, 1201.

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)	54202	4-Butylbenzoic acid; 4-n-Butylbenzoic acid	20651-71-2	C₁₁H₁₄O₂	详情	详情
(II)	54203	4-butyl-1,5-cyclohexadiene-1-carboxylic acid	n/a	C₁₁H₁₆O₂	详情	详情
(III)	54204	4-butyl-2-cyclohexene-1-carboxylic acid	n/a	C₁₁H₁₈O₂	详情	详情
(IV)	54205	methyl 4-butyl-2-cyclohexene-1-carboxylate	n/a	C₁₂H₂₀O₂	详情	详情
(V)	54206	methyl 4-butylcyclohexanecarboxylate	n/a	C₁₂H₂₂O₂	详情	详情
(V)	54246	methyl 4-butylcyclohexanecarboxylate	n/a	C₁₂H₂₂O₂	详情	详情
(VI)	54207	4-butylcyclohexanecarboxylic acid	n/a	C₁₁H₂₀O₂	详情	详情
(VI)	54247	4-butylcyclohexanecarboxylic acid	71101-89-8	C₁₁H₂₀O₂	详情	详情
(VII)	54208	trans-4-n-Butylcyclohexanecarboxylic acid	38289-28-0	C₁₁H₂₀O₂	详情	详情
(VII)	54248	4-butylcyclohexanecarboxylic acid	71101-89-8	C₁₁H₂₀O₂	详情	详情
(VIII)	54209	4-butylcyclohexanecarbonyl chloride	n/a	C₁₁H₁₉ClO	详情	详情
(VIII)	54249	4-butylcyclohexanecarbonyl chloride	n/a	C₁₁H₁₉ClO	详情	详情
(IX)	54210	17beta-Hydroxyandrost-4-en-3-one; 4-Androsten-17-beta-ol-3-one; Android; Androlin; delta4-Androsten-17beta-ol-3-one; Halotensin; Oreton; Testex; Testoderm; Testosterone; Testred; Virilon	58-22-0	C₁₉H₂₈O₂	详情	详情

Extended Information