5-(Hydroxymethyl)-2-pyrrolidinone -Drug Synthesis Database

【结构式】

【分子编号】10079

【品名】5-(Hydroxymethyl)-2-pyrrolidinone

【CA登记号】62400-75-3

【分子式】C₅H₉NO₂

【分子量】115.132

【元素组成】C 52.16% H 7.88% N 12.17% O 27.79%

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：(II)

The synthesis of [14C]-labeled vigabatrin has been described: The reduction by known methods of pyroglutamic acid (I) to the alcohol (II) and its acylation with p-toluenesulfonyl chloride gives 5-(tosyloxymethyl)pyrrolidin-2-one (III), which by reaction with [14C]-labeled sodium cyanide in hot DMF yields 5-([14C]-cyanomethyl)pyrrolidin-2-one (IV). The reduction of (VI) with H2 over Pd/Al2O3 and treatment with dimethylamine affords 5-[2-(dimethylamino)ethyl]pyrrolidin-2-one (VI), which is oxidized with H2O2 in water to the N-oxide (VI). The treatment of (VI) with K2CO3 in refluxing xylene affords 5-([14C]-vinyl)pyrrolidin-2-one (VII), which is finally submitted to ring opening with hot 5 M aqueous HCl, followed by neutralization with triethylamine.

参考文献中间体

合成目标

【1】 Wagner, E.R.; Schuster, A.J.; Synthesis of carbon-14 labeled vigabatrin. J Label Compd Radiopharm 1993, 33, 3, 213.

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)	10078	Pyrrolidonecarboxylic acid; 5-Oxo-proline; 5-Oxo-2-pyrrolidinecarboxylic acid	149-87-1	C₅H₇NO₃	详情	详情
(II)	10079	5-(Hydroxymethyl)-2-pyrrolidinone	62400-75-3	C₅H₉NO₂	详情	详情
(III)	10080	(5-Oxo-2-pyrrolidinyl)methyl phenylmethanesulfonate		C₁₂H₁₅NO₄S	详情	详情
(IV)	10081	2-(5-Oxo-2-pyrrolidinyl)acetonitrile		C₆H₈N₂O	详情	详情
(IV)	44576	2-(5-oxo-2-pyrrolidinyl)acetonitrile		C₆H₈N₂O	详情	详情
(V)	10082	5-[2-(Dimethylamino)ethyl]-2-pyrrolidinone		C₈H₁₆N₂O	详情	详情
(V)	44577	5-[2-(dimethylamino)ethyl]-2-pyrrolidinone		C₈H₁₆N₂O	详情	详情
(VI)	10083	dimethyl[2-(5-oxo-2-pyrrolidinyl)ethyl]ammoniumolate		C₈H₁₆N₂O₂	详情	详情
(VI)	44578	dimethyl[2-(5-oxo-2-pyrrolidinyl)ethyl]ammoniumolate		C₈H₁₆N₂O₂	详情	详情
(VII)	10084	5-Vinyl-2-pyrrolidinol		C₆H₁₁NO	详情	详情
(VII)	44579	5-vinyl-2-pyrrolidinol		C₆H₁₁NO	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VII)

The esterification of bromoacetic acid (I) with benzyl alcohol (II) gives the corresponding ester (III), which by reaction with triphenylphosphine (IV) in hot toluene yields the phosphonium bromide (V). The reaction of (V) with NaOH in water-dichloromethane affords benzyl(triphenylphosphoranylidene) acetate (VI), which is submitted to a Wittig condensation with 5-(hydroxymethyl)-2-pyrrolidone (VII) in the presence of Dess-Martin periodinane (DMPI) giving benzyl 3-(5-oxo-2-pyrrolidinyl)-2(E) propenoate (VIII). The acylation of (VIII) with 4-methoxybenzoyl chloride (IX) by means of triethylamine in hot toluene yields the corresponding amide (X), which is finally hydrogenated and deprotected with H2 over Pd/C in THF.

参考文献中间体

合成目标

【1】 Huang, C.C.; Synthesis of carbon-14 labeled 1-(4-methoxybenzoyl. J Label Compd Radiopharm 1987, 24, 6, 675.

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)	23660	2-Bromoacetic acid	79-08-3	C₂H₃BrO₂	详情	详情
(II)	18710	Benzyl alcohol; Phenylmethanol	100-51-6	C₇H₈O	详情	详情
(III)	12869	benzyl 2-bromoacetate	5437-45-6	C₉H₉BrO₂	详情	详情
(IV)	12437	Triphenylphosphine; Triphenyl phosphine	603-35-0	C₁₈H₁₅P	详情	详情
(V)	22667	[2-(benzyloxy)-2-oxoethyl](triphenyl)phosphonium bromide		C₂₇H₂₄BrO₂P	详情	详情
(VI)	22668	benzyl 2-(triphenylphosphoranylidene)acetate		C₂₇H₂₃O₂P	详情	详情
(VII)	10079	5-(Hydroxymethyl)-2-pyrrolidinone	62400-75-3	C₅H₉NO₂	详情	详情
(VIII)	22670	benzyl (E)-3-(5-oxo-2-pyrrolidinyl)-2-propenoate		C₁₄H₁₅NO₃	详情	详情
(IX)	22671	4-Methoxybenzoyl chloride; p-Methoxybenzoyl chloride; 4-Anisoyl chloride	100-07-2	C₈H₇ClO₂	详情	详情
(X)	22672	benzyl (E)-3-[1-(4-methoxybenzoyl)-5-oxo-2-pyrrolidinyl]-2-propenoate		C₂₂H₂₁NO₅	详情	详情

Extended Information