2-(phenoxymethyl)oxirane; oxiranylmethyl phenyl ether -Drug Synthesis Database

【结构式】

【分子编号】23932

【品名】2-(phenoxymethyl)oxirane; oxiranylmethyl phenyl ether

【CA登记号】122-60-1

【分子式】C₉H₁₀O₂

【分子量】150.1772

【元素组成】C 71.98% H 6.71% O 21.31%

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：(III)

1) The reaction of phenol (I) with epichlorohydrin (II) gives 1,2-epoxy-3-phenoxypropane (III), which is treated with isopropylamine (IV) to afford 3-(isopropylamino)-1-phenoxy-2-propanol (V). Cyclization of (V) with diethyl carbonate (VI) yields 3-isopropyl-5-(phenoxymethyloxazolidin-2-one) (VII), which is chloromethylated with formaldehyde - HCl giving 3-isopropyl-5-(4-chloromethylphenoxymethyl)oxazolidin-2-one (VIII). Etherification of (VIII) with ethylene glycol monoisopropyl ether (IX) yields the corresponding ether (XI), which is finally deprotected by alkaline hydrolysis.

参考文献中间体

合成目标

【1】 Harting, J.; et al.; Pharmacodynamic profile of the selective beta1-adrenoceptor antagonist bisoprolol. Arzneim-Forsch Drug Res 1986, 36, 2, 200.
【2】 Castaner, J.; Prous, J.; Bisoprolol fumarate. Drugs Fut 1986, 11, 10, 829.

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)	10146	Epichlorohydrin; 2-(Chloromethyl)oxirane	106-89-8	C₃H₅ClO	详情	详情
(III)	23932	2-(phenoxymethyl)oxirane; oxiranylmethyl phenyl ether	122-60-1	C₉H₁₀O₂	详情	详情
(IV)	23933	2-Propanamine; Isopropylamine	75-31-0	C₃H₉N	详情	详情
(V)	23934	1-(isopropylamino)-3-phenoxy-2-propanol		C₁₂H₁₉NO₂	详情	详情
(VI)	17470	diethyl carbonate; diethylcarbonate	105-58-8	C₅H₁₀O₃	详情	详情
(VII)	23936	3-isopropyl-5-(phenoxymethyl)-1,3-oxazolidin-2-one		C₁₃H₁₇NO₃	详情	详情
(VIII)	23937	5-[[4-(chloromethyl)phenoxy]methyl]-3-isopropyl-1,3-oxazolidin-2-one		C₁₄H₁₈ClNO₃	详情	详情
(IX)	23938	2-isopropoxy-1-ethanol	109-59-1	C₅H₁₂O₂	详情	详情
(X)	23939	5-([4-[(2-isopropoxyethoxy)methyl]phenoxy]methyl)-3-isopropyl-1,3-oxazolidin-2-one		C₁₉H₂₉NO₅	详情	详情

合成路线2

该中间体在本合成路线中的序号：(V)

1) By condensation of phenol (I) with 1-n-butoxy-2,3-epoxypropane (VII) in presence of potassium hydroxide. 2) By condensation of phenol (I) with 1-chloro-2,3-epoxypropane (II) followed either by addition of n-butanol (VI) in presence of a Lewis acid or in presence of a base (IV).

参考文献中间体

合成目标

【1】 Hoffmann, H.; et al.; Procedimiento de fabricacion de sustancias medicinalmente activas y metodo de preparacion de medicamentos de accion coleretica. ES 402799; FR 2134389; GB 1393451; US 3839587 .
【2】 Janiak, P. St.; Febuprol. Drugs Fut 1978, 3, 3, 191.

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)	10146	Epichlorohydrin; 2-(Chloromethyl)oxirane	106-89-8	C₃H₅ClO	详情	详情
(III)	33456	1-chloro-3-phenoxy-2-propanol		C₉H₁₁ClO₂	详情	详情
(IV)	33457	sodium 1-butanolate; Sodium butoxide; Sodium n-butoxide	2372-45-4	C₄H₉NaO	详情	详情
(V)	23932	2-(phenoxymethyl)oxirane; oxiranylmethyl phenyl ether	122-60-1	C₉H₁₀O₂	详情	详情
(VI)	29766	butanol; n-butanol; 1-butanol	71-36-3	C₄H₁₀O	详情	详情
(VII)	33458	2-(butoxymethyl)oxirane; butyl 2-oxiranylmethyl ether	2426-08-6	C₇H₁₄O₂	详情	详情

合成路线3

该中间体在本合成路线中的序号：(VI)

Addition of the Grignard reagent prepared from 4-bromodiphenyl ether (I) to N-Boc-4-piperidone (II) gave the 4-hydroxy-4-arylpiperidine (III). Deprotection of the Boc group of (III) with concomitant dehydration of the tertiary alcohol by means of trifluoroacetic acid afforded the tetrahydropyridine (IV), which was further hydrogenated to piperidine (V) using Pd/C as the catalyst. Condensation of pieridine (V) with phenyl glycidyl ether (VI) in refluxing isopropanol yielded the desired amino alcohol, which was finally isolated as the corresponding hydrochloride salt.

参考文献中间体

合成目标

【1】 Nakanishi, K.; Miyajima, A.; Annoura, H.; Uesugi, M.; Fukunaga, A.; Tamura, S.; Tamura-Horikawa, Y.; A novel class of Na+ and Ca2+ channel dual blockers with highly potent anti-ischemic effects. Bioorg Med Chem Lett 1999, 9, 20, 2999.

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)	35580	1-bromo-4-phenoxybenzene; 4-bromophenyl phenyl ether	101-55-3	C₁₂H₉BrO	详情	详情
(II)	18620	tert-butyl 4-oxo-1-piperidinecarboxylate;BOC-Piperidone;N-(tert-Butoxycarbonyl)-4-piperidone; N-Boc-4-piperidone	79099-07-3	C₁₀H₁₇NO₃	详情	详情
(III)	40680	tert-butyl 4-hydroxy-4-(4-phenoxyphenyl)-1-piperidinecarboxylate		C₂₂H₂₇NO₄	详情	详情
(IV)	40681	phenyl 4-(1,2,3,6-tetrahydro-4-pyridinyl)phenyl ether; 4-(4-phenoxyphenyl)-1,2,3,6-tetrahydropyridine		C₁₇H₁₇NO	详情	详情
(V)	40682	phenyl 4-(4-piperidinyl)phenyl ether; 4-(4-phenoxyphenyl)piperidine		C₁₇H₁₉NO	详情	详情
(VI)	23932	2-(phenoxymethyl)oxirane; oxiranylmethyl phenyl ether	122-60-1	C₉H₁₀O₂	详情	详情

Extended Information