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

【结构式】

【分子编号】25925

【品名】2,6-di(tert-butyl)phenol

【CA登记号】128-39-2

【分子式】C₁₄H₂₂O

【分子量】206.32808

【元素组成】C 81.5% H 10.75% O 7.75%

与该中间体有关的原料药合成路线共 4 条

合成路线1 合成路线2 合成路线3 合成路线4

合成路线1

该中间体在本合成路线中的序号：(I)

The reaction of 2,6-di-tert-butyllphenol (I) with hexamethylenetetramine (HMT) and sulfuric acid in ethyleneglycol at 130 C gives 4-hydroxy-3,5-di-tert-butylbenzaldehyde (II), which is finally condensed with 2-(3-pyridyl)acetic acid (III) by means of piperidine in dichloromethane at 130 C.

参考文献中间体

合成目标

【1】 Lazer, E.S.; Farina, P.R.; Gundel, R.H.; Wegner, C.D.; 2,6-Disubstituted-4-(2-arylethenyl)phenol 5-lipoxygenase inhibitors: Development and profile of BI-L-239. Drugs Fut 1991, 16, 7, 641.

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)	25925	2,6-di(tert-butyl)phenol	128-39-2	C₁₄H₂₂O	详情	详情
(II)	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
(III)	16168	2-(3-pyridinyl)acetic acid; 3-Pyridylacetic acid	501-81-5	C₇H₇NO₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VI)

In a related procedure, the dimethyl benzylamine (IV) was quaternized with iodomethane, and the resultant ammonium salt (V) was then condensed with the sodium salt of diphosphonate (I) (1). Other reported alkylating reagents included the bis-benzyl methyl amine (VII), prepared by Mannich reaction of methylamine with 2,6-di-t-butylphenol (VI) and formaldehyde, and the tris-benzyl amine (VIII), prepared by alkylation of ammonia with the benzyl chloride (II)

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
(IV)	62336	2,6-di(tert-butyl)-4-[(dimethylamino)methyl]phenol		C₁₇H₂₉NO	详情	详情
(V)	62338	[3,5-di(tert-butyl)-4-hydroxyphenyl]-N,N,N-trimethylmethanaminium iodide		C₁₈H₃₂INO	详情	详情
(VI)	25925	2,6-di(tert-butyl)phenol	128-39-2	C₁₄H₂₂O	详情	详情
(VII)	62339	2,6-di(tert-butyl)-4-{[[3,5-di(tert-butyl)-4-hydroxybenzyl](methyl)amino]methyl}phenol		C₃₁H₄₉NO₂	详情	详情
(VIII)	62340	4-({bis[3,5-di(tert-butyl)-4-hydroxybenzyl]amino}methyl)-2,6-di(tert-butyl)phenol		C₄₅H₆₉NO₃	详情	详情

合成路线3

该中间体在本合成路线中的序号：(I)

The 2,6-di-tert-butylphenol (I) was nitrated with nitric acid, followed by reduction with hydrogen using a platinum catalyst to afford 4-amino-2,6-di-tert-butylphenol (II). The reaction of (II) with 4-chlorobutyryl chloride (III) gave the intermediate 4-chlorobutyramide (IV), which on treatment with sodium hydride underwent cyclization to afford 1-(3,5-di-tert-butyl-4-hydroxyphenyl)pyrrolidin-2-one, BF-388.

参考文献中间体

合成目标

【1】 Naismith, R.W.; Frierson, M.R. III, Wong, S.; Lee, S.J.; BF-388. Drugs Fut 1992, 17, 10, 871.

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)	25925	2,6-di(tert-butyl)phenol	128-39-2	C₁₄H₂₂O	详情	详情
(II)	15603	4-amino-2,6-di(tert-butyl)phenol		C₁₄H₂₃NO	详情	详情
(III)	11265	4-Chlorobutanoyl chloride; 4-Chlorobutyric acid chloride	4635-59-0	C₄H₆Cl₂O	详情	详情
(IV)	15604	4-chloro-N-[3,5-di(tert-butyl)-4-hydroxyphenyl]butanamide		C₁₈H₂₈ClNO₂	详情	详情

合成路线4

该中间体在本合成路线中的序号：(I)

The reaction of 2,6-di(tert-butyl)phenol (I) with CS2 and ethyl chloroacetate gives the dithiobenzoate (II), which is treated with hydrazine in ethanol yielding the thiobenzoyl hydrazide (III). The cyclization of (III) with CS2 in refluxing ethanol affords the thiadiazolethione (IV), which is finally condensed with ethyl iodide and NaOH in THF.

参考文献中间体

合成目标

【1】 Sercel, A.D.; Connor, D.T.; Song, Y.; et al.; Synthesis, structure-activity relationships, and in vivo evaluations of substituted di-tert-butylphenols as a novel class of potent, selective, and orally active cyclooxygenase-2 inhibitors. 2. 1,3,4- and 1,2,4-thiadiazole series. J Med Chem 1999, 42, 7, 1161.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	10925	Iodoethane;ethyl iod	75-03-6	C₂H₅I	详情	详情
	16601	ethyl chloroacetate; ethyl 2-chloroacetate	105-39-5	C₄H₇ClO₂	详情	详情
(I)	25925	2,6-di(tert-butyl)phenol	128-39-2	C₁₄H₂₂O	详情	详情
(II)	25926	ethyl 2-[[3,5-di(tert-butyl)-4-hydroxybenzothioyl]sulfanyl]acetate		C₁₉H₂₈O₃S₂	详情	详情
(III)	25927	3,5-di(tert-butyl)-4-hydroxybenzenecarbothiohydrazide		C₁₅H₂₄N₂OS	详情	详情
(IV)	25928	5-[3,5-di(tert-butyl)-4-hydroxyphenyl]-1,3,4-thiadiazole-2(3H)-thione		C₁₆H₂₂N₂OS₂	详情	详情

Extended Information