2-[{2-[hydroxy(phenyl)methyl]benzyl}(methyl)amino]-1-ethanol -Drug Synthesis Database

【结构式】

【分子编号】59375

【品名】2-[{2-[hydroxy(phenyl)methyl]benzyl}(methyl)amino]-1-ethanol

【CA登记号】

【分子式】C₁₇H₂₁NO₂

【分子量】271.35928

【元素组成】C 75.25% H 7.8% N 5.16% O 11.79%

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：(VI)

The reaction of 3-phenylphthalide (I) with N-methylethanolamine (II) in refluxing benzene gives N-(2-hydroxyethyl)-2-(1-hydroxy-1-phenylmethyl)-N-methylbenzamide (III), which is cyclized by means of Ts-OH in refluxing toluene to yield 5-methyl-1-phenyl-3,4,5,6-tetrahydro-1H-2,5-benzoxazocin-6-one (IV). Finally this compound is reduced with LiAlH4 in refluxing THF to afford the target benzoxazocine. In an alternative method, the reduction of 2-benzoyl-N-(2-hydroxyethyl)-N-methylbenzamide (V) by means of sodium bis(2-methoxyethoxy)aluminum hydride in refluxing toluene gives the diol (VI), which is then cyclized by means of Ts-OH in refluxing toluene, or by means of aq. 48% HBr in hot chloroform to afford the target benzoxazocine.

参考文献中间体

合成目标

【1】 Lucero de Pablo, M.L.; Martin-Escudero Perez, U.; Izquierdo Sanjose, M.; Process for the preparation of a benzoxazine deriv. and its non-toxic salt. ES 8105723 .
【2】 Eberlin, J.W.; Process for benz[f]-2,5-oxazocines. US 3978085 .
【3】 Gimbert Roura, J.; Soler Peix, E.; Process for the preparation of benzoxazines. KE 8201564 .

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)	59371	3-Phenyl-1(3H)-isobenzofuranone; 3-Phenylphthalide	5398-11-8	C₁₄H₁₀O₂	详情	详情
(II)	13324	2-Methylaminoethanol; 2-(Methylamino)-1-ethanol	109-83-1	C₃H₉NO	详情	详情
(III)	59372	N-(2-hydroxyethyl)-2-[hydroxy(phenyl)methyl]-N-methylbenzamide		C₁₇H₁₉NO₃	详情	详情
(IV)	59373	5-methyl-1-phenyl-4,5-dihydro-1H-2,5-benzoxazocin-6(3H)-one		C₁₇H₁₇NO₂	详情	详情
(V)	59374	2-benzoyl-N-(2-hydroxyethyl)-N-methylbenzamide	24833-47-4	C₁₇H₁₇NO₃	详情	详情
(VI)	59375	2-[{2-[hydroxy(phenyl)methyl]benzyl}(methyl)amino]-1-ethanol		C₁₇H₂₁NO₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(V)

The reaction of 2-benzoylbenzoic acid (I) with refluxing SOCl2 gives the corresponding acyl chloride (II), which is condensed with 2-(methylamino)acetic acid (III) in benzene to yield the N-(2-benzoylbenzoyl)-N-methylglycine (IV). The reduction of (IV) by means of LiAlH4 in refluxing THF affords the diol (V), which is finally cyclized by means of PPA at 80 C to provide the target benzoxazocine.

参考文献中间体

合成目标

【1】 Galiano Ramos, J.A.; Verde Casanova, M.J.; Fernandez Torija, C. (Instituto de Investigacion y Desarrollo Quimico Biologico SA); Process for the preparation of 1-methyl-5-phenyl-aza-4-oxo-6,7-benzocyclooctane. ES 8104800 .

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)	59365	2-benzophenone carboxylic acid; 2-Benzoylbenzoic acid; 2-Carboxybenzophenone; Benzophenone-2-carboxylic acid; O-benzoylbenzoic acid	85-52-9	C₁₄H₁₀O₃	详情	详情
(II)	59366	2-benzoylbenzoyl chloride		C₁₄H₉ClO₂	详情	详情
(III)	10429	N-Methylglycine; Sarcosine; 2-(Methylamino)acetic acid	107-97-1	C₃H₇NO₂	详情	详情
(IV)	59376	2-[(2-benzoylbenzoyl)(methyl)amino]acetic acid		C₁₇H₁₅NO₄	详情	详情
(V)	59375	2-[{2-[hydroxy(phenyl)methyl]benzyl}(methyl)amino]-1-ethanol		C₁₇H₂₁NO₂	详情	详情

合成路线3

该中间体在本合成路线中的序号：(VI)

The reaction of 2-benzoylbenzoic acid (I) with PCl3 in dichloromethane gives the corresponding acyl chloride (II), which is condensed with N-methylethanolamine (III) by means of TEA In dichloroethane to yield the amide (IV). The reaction of (IV) with PCl3 in dichloroethane affords the 2-chloroethylamide (V), which is reduced with NaBH4 and A-OH in dichloromethane to provide the diol (VI). Finally, this compound is cyclized by means of aq. HBr in dichloroethane to give the target benzoxazocine.

参考文献中间体

合成目标

【1】 Watson, P.G.; Process for the preparation of 2-[N-(2-hydroxyethyl)-N-lower alkylaminomethyl]benzhydrols. US 4208349 .
【2】 Watson, P.G.; Process for the preparation of 2-[N-(2-hydroxyethyl)-N-lower alkylaminomethyl)benzhydrols. GB 1586578 .

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)	59365	2-benzophenone carboxylic acid; 2-Benzoylbenzoic acid; 2-Carboxybenzophenone; Benzophenone-2-carboxylic acid; O-benzoylbenzoic acid	85-52-9	C₁₄H₁₀O₃	详情	详情
(II)	59366	2-benzoylbenzoyl chloride		C₁₄H₉ClO₂	详情	详情
(III)	13324	2-Methylaminoethanol; 2-(Methylamino)-1-ethanol	109-83-1	C₃H₉NO	详情	详情
(IV)	59374	2-benzoyl-N-(2-hydroxyethyl)-N-methylbenzamide	24833-47-4	C₁₇H₁₇NO₃	详情	详情
(V)	59377	2-benzoyl-N-(2-chloroethyl)-N-methylbenzamide		C₁₇H₁₆ClNO₂	详情	详情
(VI)	59375	2-[{2-[hydroxy(phenyl)methyl]benzyl}(methyl)amino]-1-ethanol		C₁₇H₂₁NO₂	详情	详情

Extended Information