2,6-di(tert-butyl)-4-(hydroxymethyl)phenol -Drug Synthesis Database

【结构式】

【分子编号】37706

【品名】2,6-di(tert-butyl)-4-(hydroxymethyl)phenol

【CA登记号】88-26-6

【分子式】C₁₅H₂₄O₂

【分子量】236.35436

【元素组成】C 76.23% H 10.23% O 13.54%

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：(III)

Alternatively, tetraisopropyl methylenediphosphonate (I) was alkylated with the benzyl alcohol (III) or with the dimethyl benzylamine (IV) in the presence of strong bases such as NaH or NaO-t-Bu

参考文献中间体

合成目标

【1】 Grinter, T.J.; Harris, M.A.; Hayler, J.D.; Negus, A. (Ilex Oncology Research-Europe SA); A process for the preparation of diphosphonate derivs.. WO 9731004 .

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)	27980	Diisopropyl (diisopropoxyphosphoryl)methylphosphonate; Tetraisopropyl methylenediphosphonate	1660-95-3	C₁₃H₃₀O₆P₂	详情	详情
(III)	37706	2,6-di(tert-butyl)-4-(hydroxymethyl)phenol	88-26-6	C₁₅H₂₄O₂	详情	详情
(IV)	62336	2,6-di(tert-butyl)-4-[(dimethylamino)methyl]phenol		C₁₇H₂₉NO	详情	详情

合成路线2

该中间体在本合成路线中的序号：(III)

In a further method, condensation of benzyl alcohol (III) with methanol in the presence of a catalytic amount of HCl afforded the corresponding methyl ether (IX), which was then reacted with diphosphonate (I) in the presence of NaH to furnish the target arylethyl diphosphonate (1). Optionally, diphosphonate (I) was condensed with the benzyl acetate ester (X), prepared from benzyl chloride (II) and potassium acetate in acetone

参考文献中间体

合成目标

【1】 Grinter, T.J.; Harris, M.A.; Hayler, J.D.; Negus, A. (Ilex Oncology Research-Europe SA); A process for the preparation of diphosphonate derivs.. WO 9731004 .

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)	27980	Diisopropyl (diisopropoxyphosphoryl)methylphosphonate; Tetraisopropyl methylenediphosphonate	1660-95-3	C₁₃H₃₀O₆P₂	详情	详情
(II)	62335	2,6-di(tert-butyl)-4-(chloromethyl)phenol		C₁₅H₂₃ClO	详情	详情
(III)	37706	2,6-di(tert-butyl)-4-(hydroxymethyl)phenol	88-26-6	C₁₅H₂₄O₂	详情	详情
(IX)	62341	2,6-di(tert-butyl)-4-(methoxymethyl)phenol		C₁₆H₂₆O₂	详情	详情
(X)	62342	3,5-di(tert-butyl)-4-hydroxybenzyl acetate		C₁₇H₂₆O₃	详情	详情

合成路线3

该中间体在本合成路线中的序号：(VI)

Alkylation of ethyl 1-piperazinecarboxylate (I) with 2-bromo-4'-chloroacetophenone (II) afforded disubstituted piperazine (III). Further cleavage of the carbamate group of (III) in refluxing HCl produced piperazine (IV). Bromide (VII) was prepared by reduction of 3,5-di-tert-butyl-4-hydroxybenzaldehyde (V) with NaBH4, followed by treatment of the resulting alcohol (VI) with PBr3. Piperazine (IV) was then condensed with bromide (VII) to give adduct (VIII). Finally, ketone reduction using LiAlH4 furnished the title alcohol.

参考文献中间体

合成目标

【1】 Collis, M.P.; Robertson, A.D.; Kenche, V.B.; Jackson, W.R.; Jarrott, B.; Beart, P.M. (Monash University); Arylalkylpiperazine cpds. as antioxidants. JP 2000510126; WO 9743259 .

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)	24694	N-ethoxycarbonylpiperidine; Ethyl 1-piperazinecarboxylate; N-Ethoxycarbonyl piperazine; N-Carbethoxy piperazine	120-43-4	C₇H₁₄N₂O₂	详情	详情
(II)	16720	2-bromo-1-(4-chlorophenyl)-1-ethanone; 2-Bromo-4'-chloroacetophenone	536-38-9	C₈H₆BrClO	详情	详情
(III)	37704	ethyl 4-[2-(4-chlorophenyl)-2-oxoethyl]-1-piperazinecarboxylate		C₁₅H₁₉ClN₂O₃	详情	详情
(IV)	37705	1-(4-chlorophenyl)-2-(1-piperazinyl)-1-ethanone		C₁₂H₁₅ClN₂O	详情	详情
(V)	14875	3,5-Bis(1,1-dimethylethyl)-4-hydroxybenzaldehyde; 3,5-di(tert-butyl)-4-hydroxybenzaldehyde; 3,5-Di-tert-butyl-4-hydroxybenzaldehyde	1620-98-0	C₁₅H₂₂O₂	详情	详情
(VI)	37706	2,6-di(tert-butyl)-4-(hydroxymethyl)phenol	88-26-6	C₁₅H₂₄O₂	详情	详情
(VII)	37707	4-(bromomethyl)-2,6-di(tert-butyl)phenol		C₁₅H₂₃BrO	详情	详情
(VIII)	37708	1-(4-chlorophenyl)-2-[4-[3,5-di(tert-butyl)-4-hydroxybenzyl]-1-piperazinyl]-1-ethanone		C₂₇H₃₇ClN₂O₂	详情	详情

Extended Information