2-[4-(2-oxiranylmethoxy)phenyl]acetamide -Drug Synthesis Database

【结构式】

【分子编号】32755

【品名】2-[4-(2-oxiranylmethoxy)phenyl]acetamide

【CA登记号】

【分子式】C₁₁H₁₃NO₃

【分子量】207.22916

【元素组成】C 63.76% H 6.32% N 6.76% O 23.16%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(VI)

This compound has been obtained by two related ways: 1) The reaction of phenol (I) with formaldehyde gives 4-(hydroxymethyl)phenol (II), which is treated with NaCN in hot DMF to yield 2-(4-hydroxyphenyl)acetonitrile (III). The hydrolysis of (III) in refluxing ethanol/water, catalyzed by a Pt catalyst affords the corresponding acetamide (IV), which is condensed with an excess of hot epichlorohydrin (V) by means of piperidine gives 2-[4-(2-oxiranylmethoxy)phenyl]acetamide (VI). Finally, the oxirane ring of (VI) is opened with isopropylamine in methanol. 2)The condensation of acetonitrile (III) with epichlorohydrin (V) as before gives the 2-[4-(2-oxiranylmethoxy)phenyl]acetonitrile (VIII), which is treated with isopropylamine (VII) in methanol yielding 2-[4-[2-hydroxy-3-(isopropylamino)propoxy]phenyl]acetonitrile (IX). Finally, this compound is hydrolyzed with refluxing ethanol/water catalyzed by a Pt catalyst as before to afford the target acetamide.

参考文献中间体

合成目标

【1】 Akisanya, J.; et al.; A synthesis of atenolol using a nitrile hydration catalyst. Org Process Res Dev 1998, 2, 4, 274.

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)	23540	Phenol	108-95-2	C₆H₆O	详情	详情
(II)	29474	4-(hydroxymethyl)phenol; 4-hydroxyphenylmethanol 4-hydroxybenzenemethanol; 4-Hydroxybenzyl alcohol	623-05-2	C₇H₈O₂	详情	详情
(III)	32753	2-(4-hydroxyphenyl)acetonitrile; 4-Hydroxybenzyl cyanide	14191-95-8	C₈H₇NO	详情	详情
(IV)	32754	p-Hydroxyphenylacetamide; 2-(4-hydroxyphenyl)acetamide; 4-Hydroxybenzeneacetamide; 4-Hydroxyphenylacetamide	17194-82-0	C₈H₉NO₂	详情	详情
(V)	10146	Epichlorohydrin; 2-(Chloromethyl)oxirane	106-89-8	C₃H₅ClO	详情	详情
(VI)	32755	2-[4-(2-oxiranylmethoxy)phenyl]acetamide		C₁₁H₁₃NO₃	详情	详情
(VII)	23933	2-Propanamine; Isopropylamine	75-31-0	C₃H₉N	详情	详情
(VIII)	32756	2-[4-(2-oxiranylmethoxy)phenyl]acetonitrile		C₁₁H₁₁NO₂	详情	详情
(IX)	32757	2-[4-[2-hydroxy-3-(isopropylamino)propoxy]phenyl]acetonitrile		C₁₄H₂₀N₂O₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(III)

Prepared in two steps by condensation of p-hydroxyphenylacetamide (I) and epichlorhydrine (II) with piperidine as catalyst, giving 1-(p-carbamoylmethylphenoxy)-2,3-epoxypropane (III), m.p. 158-60 C, followed by reaction of the epoxy ring with isopropylamine (IV).

参考文献中间体

合成目标

【1】 Barret, A.; et al.; Alkanolaminderivate. CH 547257; CH 553747; DE 2007751; ES 376788; FR 2034561 .
【2】 Castaner, J.; Atenolol. Drugs Fut 1976, 1, 1, 7.

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)	32754	p-Hydroxyphenylacetamide; 2-(4-hydroxyphenyl)acetamide; 4-Hydroxybenzeneacetamide; 4-Hydroxyphenylacetamide	17194-82-0	C₈H₉NO₂	详情	详情
(II)	10146	Epichlorohydrin; 2-(Chloromethyl)oxirane	106-89-8	C₃H₅ClO	详情	详情
(III)	32755	2-[4-(2-oxiranylmethoxy)phenyl]acetamide		C₁₁H₁₃NO₃	详情	详情
(IV)	23933	2-Propanamine; Isopropylamine	75-31-0	C₃H₉N	详情	详情

Extended Information