3-Hydroxybenzyl alcohol; 3-(hydroxymethyl)phenol -Drug Synthesis Database

【结构式】

【分子编号】17296

【品名】3-Hydroxybenzyl alcohol; 3-(hydroxymethyl)phenol

【CA登记号】620-24-6

【分子式】C₇H₈O₂

【分子量】124.13932

【元素组成】C 67.73% H 6.5% O 25.78%

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：(I)

A mixture of 3-hydroxybenzyl alcohol (I) with 48% hydrobromic acid in dichloromethane is stirred at room temperature to give the corresponding benzyl bromide (II), which is immediately dissolved in acetonitrile. Silver nitrate is added proportionally to the crude solution (II) at room temperature to obtain derivative (III). A mixture of (III), potassium carbonate and ethyl acetate is cooled under nitrogen at 0 C and slowly treated with a solution of O-acetylsalicyloyl chloride (IV) in ethyl acetate to yield crude NCX-4016. The pure product is obtained by crystallization from isopropyl ether. The three-step prepaation is described in the Scheme 25203601a.

参考文献中间体

合成目标

【1】 Cirino, G.; et al.; NCX-4016. Drugs Fut 1997, 22, 11, 1231.

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)	17296	3-Hydroxybenzyl alcohol; 3-(hydroxymethyl)phenol	620-24-6	C₇H₈O₂	详情	详情
(II)	17297	3-(bromomethyl)phenol		C₇H₇BrO	详情	详情
(III)	17298	3-[(nitrooxy)methyl]phenol		C₇H₇NO₄	详情	详情
(IV)	16900	2-(chlorocarbonyl)phenyl acetate; Acetylsalicyloyl chloride	5538-51-2	C₉H₇ClO₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

Alkylation of 3-hydroxybenzyl alcohol (II) with 2-chloromethylquinazoline (I) in the presence of K2CO3 and tetrabutylammonium bromide provided ether (III). The hydroxyl group of (III) was converted to chloride (IV) by treatment with thionyl chloride. Finally, alkylation of hydroxybenzothiazinone (V) with chloride (IV) yielded the title compound.

参考文献中间体

合成目标

【1】 Tamura, M.; Tohma, T.; Onogi, K.; et al.; VUF-K-8707 and analogs, non-acidic leukotriene D4 receptor antagonists. 15th European Federation for Medicinal Chemistry International Symposium on Medicinal Chemistry (Sept 6 1998, Edinburgh) 1998, Abst P.226.
【2】 Timmerman, H.; Zhang, M.; Onogi, K.; Tamura, M.; Toma, T.; Wada, Y. (Kowa Co., Ltd.); Heteroaryl substd. phenylene derivs., their preparation and their use a leukotriene receptor antagonists. EP 0799826; JP 1997323975; US 5756518; US 5885987; US 6011033 .

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)	28285	2-(chloromethyl)quinazoline		C₉H₇ClN₂	详情	详情
(II)	17296	3-Hydroxybenzyl alcohol; 3-(hydroxymethyl)phenol	620-24-6	C₇H₈O₂	详情	详情
(III)	28286	[3-(2-quinazolinylmethoxy)phenyl]methanol		C₁₆H₁₄N₂O₂	详情	详情
(IV)	28287	2-[[3-(chloromethyl)phenoxy]methyl]quinazoline		C₁₆H₁₃ClN₂O	详情	详情
(V)	28290	7-hydroxy-2H-1,4-benzothiazin-3(4H)-one		C₈H₇NO₂S	详情	详情

合成路线3

该中间体在本合成路线中的序号：(II)

Alkylation of 3-hydroxybenzyl alcohol (II) with benzimidazolylmethyl chloride (I) in the presence of K2CO3 and tetrabutylammonium bromide provided ether (III). The hydroxyl group of (III) was converted to chloride (IV) by treatment with thionyl chloride. Finally, alkylation of hydroxybenzothiazinone (V) with chloride (IV) yielded the title compound.

参考文献中间体

合成目标

【1】 Tamura, M.; Tohma, T.; Onogi, K.; et al.; VUF-K-8707 and analogs, non-acidic leukotriene D4 receptor antagonists. 15th European Federation for Medicinal Chemistry International Symposium on Medicinal Chemistry (Sept 6 1998, Edinburgh) 1998, Abst P.226.
【2】 Timmerman, H.; Zhang, M.; Onogi, K.; Tamura, M.; Toma, T.; Wada, Y. (Kowa Co., Ltd.); Heteroaryl substd. phenylene derivs., their preparation and their use a leukotriene receptor antagonists. EP 0799826; JP 1997323975; US 5756518; US 5885987; US 6011033 .

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)	28288	2-(chloromethyl)-1-(2-ethoxyethyl)-1H-benzimidazole		C₁₂H₁₅ClN₂O	详情	详情
(II)	17296	3-Hydroxybenzyl alcohol; 3-(hydroxymethyl)phenol	620-24-6	C₇H₈O₂	详情	详情
(III)	28289	(3-[[1-(2-ethoxyethyl)-1H-benzimidazol-2-yl]methoxy]phenyl)methanol		C₁₉H₂₂N₂O₃	详情	详情
(IV)	28291	2-[[3-(chloromethyl)phenoxy]methyl]-1-(2-ethoxyethyl)-1H-benzimidazole		C₁₉H₂₁ClN₂O₂	详情	详情
(V)	28290	7-hydroxy-2H-1,4-benzothiazin-3(4H)-one		C₈H₇NO₂S	详情	详情

Extended Information