1-phenyl-3-oxabicyclo[3.1.0]hexan-2-one -Drug Synthesis Database

【结构式】

【分子编号】28144

【品名】1-phenyl-3-oxabicyclo[3.1.0]hexan-2-one

【CA登记号】

【分子式】C₁₁H₁₀O₂

【分子量】174.1992

【元素组成】C 75.84% H 5.79% O 18.37%

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：(I)

This compound can be prepared in several ways from the lactone (I), which is obtained by treatment of benzyl cyanide (A) and epichlorhydrin (B) with sodium amide: 1) The opening of lactone (I) with SOBr2-ethanol gives a bromo ester, which is treated successively by ammonia and sodium hydroxide to yield the amino acid (II). The reaction of (II) with SOCl2 and diethylamine in ethanol gives the final product, which is converted to the hydrochloric salt by treatment with HCl ethanol. 2) Lactone (I), opened with 33% HBr-AcOH, gives the bromo acid (III), which is treated by SOCl2 and then diethylamine in ethanol. The bromoamide (IV) reacts with potassium phthalimide and is deprotected by hydrazine or methylamine to yield, after salification, title compound. 3) Lactone (I) is treated by potassium phthalimide and then SOCl2 and diethylamine in EtOH to give compound (V), treated as above. 4) Bromoamide (IV) can be treated by hexamethylenetetramine in butanol and hydrolyzed by refluxing with 15% HCl in ethanol.

参考文献中间体

合成目标

【1】 Kasama, S.; et al.; Synthesis 1978, 4, 10, 304.
【2】 Patoiseau, J.-F.; Mouzin, G.; Bonnaud, B.; Cousse, H. (Pierre Fabre Medicament); Process for the preparation of (Z)-1-phenyl-1-diethylaminocarbonyl-2-aminomethyl-cyclopropane. EP 0200638; FR 2581059 .
【3】 Cousse, H.; Hascoet, P. (Pierre Fabre Medicament); Industrial process for the production of midalcipran. FR 2581060 .
【4】 Mouzin, G.; Cousse, H.; Bonnaud, B.; Morre, M.; Stenger, A. (Pierre Fabre Médicament); 1-Aryl-2-aminomethyl cyclopropane carboxyamide (Z) deivatives and their use as useful drugs in the treatment of disturbances of the central nervous system. EP 0068999; FR 2508035; JP 58004752; US 4478836 .
【5】 Briley, M.; Midalcipran Hydrochloride. Drugs Fut 1986, 11, 1, 21.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(B)	10146	Epichlorohydrin; 2-(Chloromethyl)oxirane	106-89-8	C₃H₅ClO	详情	详情
(A)	17046	Phenylacetonitrile; 2-phenylacetonitrile; Benzyl cyanide	140-29-4	C₈H₇N	详情	详情
(F)	27890	Potassium phthalimide	1074-82-4	C₈H₄KNO₂	详情	详情
(G)	28148	1-([2-[(diethylamino)carbonyl]-2-phenylcyclopropyl]methyl)-3,5,7-triaza-1-azoniatricyclo[3.3.1.1(3,7)]decane		C₂₁H₃₂N₅O	详情	详情
(E)	28150	2-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]-1-phenylcyclopropanecarboxylic acid		C₁₉H₁₅NO₄	详情	详情
(D)	28151	2-(hydroxymethyl)-1-phenylcyclopropanecarboxylic acid		C₁₁H₁₂O₃	详情	详情
(I)	28144	1-phenyl-3-oxabicyclo[3.1.0]hexan-2-one		C₁₁H₁₀O₂	详情	详情
(II)	28145	2-(aminomethyl)-1-phenylcyclopropanecarboxylic acid		C₁₁H₁₃NO₂	详情	详情
(III)	28146	2-(bromomethyl)-1-phenylcyclopropanecarboxylic acid		C₁₁H₁₁BrO₂	详情	详情
(IV)	28147	2-(bromomethyl)-N,N-diethyl-1-phenylcyclopropanecarboxamide		C₁₅H₂₀BrNO	详情	详情
(V)	28149	2-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]-N,N-diethyl-1-phenylcyclopropanecarboxamide		C₂₃H₂₄N₂O₃	详情	详情
(C)	28143	2-(hydroxymethyl)-1-phenylcyclopropanecarboxylic acid		C₁₁H₁₂O₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

Opening of the known lactone (I) with HBr in HOAc produces the racemic cis bromo-acid (II). Acid (II) is then converted to the corresponding methyl ester (III) by chlorination with SOCl2, followed by treatment with methanolic HCl. Acylation of 1-adamantanamine (IV) with ethyl formate yields the formamide (V), which is subsequently reduced to the N-methyl amine (VI) employing LiAlH4 in THF. Finally, alkylation of the secondary amine (VI) with bromo ester (III) in the presence of NaHCO3 in hot DMF gives rise to the title compound.

参考文献中间体

合成目标

【1】 Ronsisvalle, G.; et al.; Substituted 1-phenyl-2-cyclopropylmethylamines with high affinity and selectively for sigma sites. Bioorg Med Chem 2000, 8, 6, 1503.

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)	28144	1-phenyl-3-oxabicyclo[3.1.0]hexan-2-one		C₁₁H₁₀O₂	详情	详情
(II)	59006	(1S,2R)-2-(bromomethyl)-1-phenylcyclopropanecarboxylic acid		C₁₁H₁₁BrO₂	详情	详情
(III)	59007	methyl (1S,2R)-2-(bromomethyl)-1-phenylcyclopropanecarboxylate		C₁₂H₁₃BrO₂	详情	详情
(IV)	53978	1-Adamantanamine; 1-Adamantylamine; 1-Aminoadamantane	768-94-5	C₁₀H₁₇N	详情	详情
(V)	59008	1-adamantylformamide		C₁₁H₁₇NO	详情	详情
(VI)	59009	N-(1-adamantyl)-N-methylamine; N-methyl-1-adamantanamine		C₁₁H₁₉N	详情	详情

Extended Information