2-hydroxybenzoyl chloride -Drug Synthesis Database

【结构式】

【分子编号】32668

【品名】2-hydroxybenzoyl chloride

【CA登记号】

【分子式】C₇H₅ClO₂

【分子量】156.5682

【元素组成】C 53.7% H 3.22% Cl 22.64% O 20.44%

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)

It is prepared by treatment of 2-hydroxybenzoic acid (I) with phosphorous pentachloride. The reaction involves a first stage in which (I) is converted by PCl5 to the corresponding acyl chloride (II) upon release of phosphorous oxychloride, which reacts immediately with the free phenolic group of (II), giving rise to the acid trichloride (III). In a second stage, (III) is hydrolyzed with enough water to give the 2-phosphonoxybenzoic acid (IV). The reaction is carried out in a one-step process, which involves chlorination, phosphonation and hydrolysis, the isolation of the intermediate (III) being unnecessary. The final product is recovered from the reaction mixture by precipitation with a suitable inert organic solvent and is submitted to further purification.

参考文献中间体

合成目标

【1】 Marin, A.; Francia, E.; Procedimiento de obtencion del acido 2-fosfonoxibenzoico y sales del mismo. DE 2641526; ES 460645 .
【2】 Francia, E.; Garcia-Rafanell, J.; Marin, A.; Fosfosal. Drugs Fut 1980, 5, 6, 290.

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)	15240	2-Hydroxybenzoic acid; Salicylic acid	69-72-7	C₇H₆O₃	详情	详情
(II)	32668	2-hydroxybenzoyl chloride		C₇H₅ClO₂	详情	详情
(III)	32669	2-[(dichlorophosphoryl)oxy]benzoyl chloride		C₇H₄Cl₃O₃P	详情	详情

合成路线2

该中间体在本合成路线中的序号：(III)

The silylation of 8-aminooctanoic acid (I) with Tms-Cl in dichloromethane gives the disilylated compound (II), which is treated with 2-hydroxybenzoyl chloride (III) and TEA to yield the corresponding silylated amide (IV). Finally, this compound is desilylated with NaOH to afford the target sodium salt.

参考文献中间体

合成目标

【1】 Baughman, R.A.; Salo-Kostmayer, S.; O'Toole, D.; Rosado-Gray, C.; Tai, M.; Mercogliano, F.; Leone-Bay, A.; Freeman, J.; Studies directed at the use of a parallel synthesis matrix to increase throughput in an in vivo assay. J Med Chem 2000, 43, 19, 3573.

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)	47828	8-aminooctanoic acid	1002-57-9	C₈H₁₇NO₂	详情	详情
(II)	47829	trimethylsilyl 8-[(trimethylsilyl)amino]octanoate		C₁₄H₃₃NO₂Si₂	详情	详情
(III)	32668	2-hydroxybenzoyl chloride		C₇H₅ClO₂	详情	详情
(IV)	47830	trimethylsilyl 8-[(2-hydroxybenzoyl)amino]octanoate		C₁₈H₂₉NO₄Si	详情	详情

合成路线3

该中间体在本合成路线中的序号：(II)

Cyclization of salicylamide (I) with salicyloyl chloride (II) by heating at 170 oC provides 2-(2-hydroxyphenyl)-benz[e][1,3]oxazin-4-one (III), which is finally cyclized with 4-hydrazinobenzoic acid (IV) in refluxing ethanol.

参考文献中间体

合成目标

【1】 Lattmann, R.; Acklin, P. (Novartis AG); Substd. 3,5-diphenyl-1,2,4-triazoles and their use as pharmaceutical metal chelators. EP 0914118; JP 2000507601; WO 9749395 .
【2】 McIntyre, J.A., Castaner, J., Mealy, N.E., Bayes, M.; Deferasirox. Drugs Fut 2004, 29 (4): 331

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)	14652	salicylamide	65-45-2	C₇H₇NO₂	详情	详情
(II)	32668	2-hydroxybenzoyl chloride		C₇H₅ClO₂	详情	详情
(III)	49109	2-(2-hydroxyphenyl)-4H-1,3-benzoxazin-4-one		C₁₄H₉NO₃	详情	详情
(IV)	49110	4-Carboxyphenyl hydrazine; p-Hydrazinobenzoic acid; p-Carboxyphenyl hydrazine; 4-Hydrazinobenzoic acid	619-67-0	C₇H₈N₂O₂	详情	详情

Extended Information