methyl 4,4-bis(4-hydroxyphenyl)pentanoate -Drug Synthesis Database

【结构式】

【分子编号】22392

【品名】methyl 4,4-bis(4-hydroxyphenyl)pentanoate

【CA登记号】

【分子式】C₁₈H₂₀O₄

【分子量】300.3544

【元素组成】C 71.98% H 6.71% O 21.31%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(II)

Esterification of 4,4-bis(4-hydroxyphenyl)pentanoic acid (I) was performed in a refluxing methanolic solution, using sulfuric acid as the catalyst. The resulting methyl ester (II) was alkylated on both phenolic groups with 2-(chloromethyl)quinoline hydrochloride (III) in the presence of potassium carbonate to afford IV. Hydrolysis of this ester (IV) with NaOH in a refluxing mixture of dioxane-methanol yielded acid (V), which was then converted into the sodium salt on treatment with one equivalent of NaOH in dioxane-methanol.

参考文献中间体

合成目标

【1】 Brooks, C.D.W.; Bhatia, P.; Kolasa, T.; Stewart, A.O.; Gunn, D.E.; Craig, R.A. (Abbott Laboratories Inc.); Symmetrical bis-heteroarylmethoxyphenylalkyl carboxylates as inhibitors of leukotriene biosynthesis. EP 0862557; US 5795900; WO 9712867 .

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)	22391	4,4-bis(4-hydroxyphenyl)pentanoic acid	126-00-1	C₁₇H₁₈O₄	详情	详情
(II)	22392	methyl 4,4-bis(4-hydroxyphenyl)pentanoate		C₁₈H₂₀O₄	详情	详情
(III)	13162	2-(Chloromethyl)quinoline; alpha-Chloroquinaldine	4377-41-7	C₁₀H₈ClN	详情	详情
(IV)	22394	methyl 4,4-bis[4-(2-quinolinylmethoxy)phenyl]pentanoate		C₃₈H₃₄N₂O₄	详情	详情
(V)	22395	4,4-bis[4-(2-quinolinylmethoxy)phenyl]pentanoic acid		C₃₇H₃₂N₂O₄	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 reaction of phenol (I) with 4-oxopentanoic acid (II) by means of H2SO4 gives 4,4-bis(4-hydroxyphenyl)pentanoic acid (III), which is esterified with MeOH and H2SO4 to yield the methyl pentanoate (IV). The condensation of (IV) with 2-(chloromethyl)quinoline (V) by means of K2CO3 in DMF affords the adduct (VI), which is finally hydrolyzed with NaOH in methanol/dioxane to provide the target sodium salt. Alternatively, the intermediate methyl pentanoate (IV) can also be obtained by direct condensation of phenol (I) with methyl 4-oxopentanoate (VII) by means of H2SO4 as before.

参考文献中间体

合成目标

【1】 Gunn, D.E.; Bhatia, P.; Kolasa, T.; et al.; Symmetrical bis(heteroarylmethoxyphenyl)alkylcarboxylic acids as inhibitors of leukotriene biosynthesis. J Med Chem 2000, 43, 17, 3322.

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)	23540	Phenol	108-95-2	C₆H₆O	详情	详情
(II)	36170	4-oxopentanoic acid	123-76-2	C₅H₈O₃	详情	详情
(III)	22391	4,4-bis(4-hydroxyphenyl)pentanoic acid	126-00-1	C₁₇H₁₈O₄	详情	详情
(IV)	22392	methyl 4,4-bis(4-hydroxyphenyl)pentanoate		C₁₈H₂₀O₄	详情	详情
(V)	13162	2-(Chloromethyl)quinoline; alpha-Chloroquinaldine	4377-41-7	C₁₀H₈ClN	详情	详情
(VI)	22394	methyl 4,4-bis[4-(2-quinolinylmethoxy)phenyl]pentanoate		C₃₈H₃₄N₂O₄	详情	详情
(VII)	50960	Methyl levulinate		C₆H₁₀O₃	详情	详情

合成路线3

该中间体在本合成路线中的序号：(II)

The esterification of 4,4-bis(4-hydroxyphenyl)pentanoic acid (I) with diazomethane in ethyl ether/methanol gives the methyl ester (II), which is treated with phenylmagnesium bromide in THF to yield 4,4-bis(4-hydroxyphenyl)-1,1-diphenyl-1-pentanol (III). The reduction of (III) with H2 over Pd/C in methanol affords 4,4-bis(4-hydroxyphenyl)-1,1-diphenylpentane (IV), which is finally condensed with azepane (V) and formaldehyde in hot ethanol/water.

参考文献中间体

合成目标

【1】 Yuen, P.-w.; Malone, T.C.; Tarczy-Hornoch, K.; Rock, D.M.; Szoke, B.; Stoehr, S.; Schelkun, R.M.; Synthesis and biological activity of substituted bis-(4-hydroxyphenyl)methanes as N-type calcium channel blockers. Bioorg Med Chem Lett 1999, 9, 16, 2447.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(A)	17616	bromo(phenyl)magnesium; Phenyl Magnesium Bromide	100-58-3	C₆H₅BrMg	详情	详情
(I)	22391	4,4-bis(4-hydroxyphenyl)pentanoic acid	126-00-1	C₁₇H₁₈O₄	详情	详情
(II)	22392	methyl 4,4-bis(4-hydroxyphenyl)pentanoate		C₁₈H₂₀O₄	详情	详情
(III)	31669	4-[4-hydroxy-1-(4-hydroxyphenyl)-1-methyl-4,4-diphenylbutyl]phenol		C₂₉H₂₈O₃	详情	详情
(IV)	31670	4-[1-(4-hydroxyphenyl)-1-methyl-4,4-diphenylbutyl]phenol		C₂₉H₂₈O₂	详情	详情
(V)	18672	azepane	111-49-9	C₆H₁₃N	详情	详情

Extended Information