(1S,5R)-1-phenyl-3-oxabicyclo[3.1.0]hexan-2-one -Drug Synthesis Database

【结构式】

【分子编号】61470

【品名】(1S,5R)-1-phenyl-3-oxabicyclo[3.1.0]hexan-2-one

【CA登记号】63106-93-4

【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 7 条

合成路线1 合成路线2 合成路线3 合成路线4 合成路线5 合成路线6 合成路线7

合成路线1

该中间体在本合成路线中的序号：(I)

The title compound is synthesized from the optically active lactone (I). Aluminum chloride-catalyzed aminolysis of (I) with dipropylamine affords the hydroxy amide (II). Subsequent Swern oxidation of the alcohol function of (II) leads to aldehyde (III). Addition of ethylmagnesium bromide to aldehyde (III) then stereoselectively provides the (S)-alcohol adduct (IV). Introduction of an azido group in (IV) by using a Mitsunobu-type reaction leads to configuration-retained azide (V). This is finally reduced to the desired amine by catalytic hydrogenation in the presence of Pd/C

参考文献中间体

合成目标

【1】 Kazuta, Y.; et al.; Synthesis of (1S,2R)-1-phenyl-2-[(S)-1-aminopropyl]-N, N-diethylcyclopropanecarboxamide (PPDC) derivatives modified at the carbamoyl moiety as a new class of NMDA receptor antagonists. Bioorg. Med. Chem. 2002, 10, 6, 1777.

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)	61470	(1S,5R)-1-phenyl-3-oxabicyclo[3.1.0]hexan-2-one	63106-93-4	C₁₁H₁₀O₂	详情	详情
(II)	61471	(1S,2R)-2-(hydroxymethyl)-1-phenyl-N,N-dipropylcyclopropanecarboxamide		C₁₇H₂₅NO₂	详情	详情
(III)	61472	(1S,2R)-2-formyl-1-phenyl-N,N-dipropylcyclopropanecarboxamide		C₁₇H₂₃NO₂	详情	详情
(IV)	61473	(1S,2R)-2-[(1S)-1-hydroxypropyl]-1-phenyl-N,N-dipropylcyclopropanecarboxamide		C₁₉H₂₉NO₂	详情	详情
(V)	61474	(1S,2R)-2-[(1S)-1-azidopropyl]-1-phenyl-N,N-dipropylcyclopropanecarboxamide		C₁₉H₂₈N₄O	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IV)

参考文献中间体

合成目标

【1】王晓琴，徐鹏，顾君琳，等.2004.盐酸米那普仑右旋异构体的合成。中国医药工业杂志，35（5）：259～260.
【2】 Bonnaud B, Cousse H, Mouzin G, et al. 1987. 1-Aryl-2-(aminomethyl) cyclopropanecarboxylic acid derivatives. A new series of potential antidepressants. J Med Chem, 30: 318～325.

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)	17046	Phenylacetonitrile; 2-phenylacetonitrile; Benzyl cyanide	140-29-4	C₈H₇N	详情	详情
(I)	17046	Phenylacetonitrile; 2-phenylacetonitrile; Benzyl cyanide	140-29-4	C₈H₇N	详情	详情
(II)	38067	(2R)-2-(Chloromethyl)oxirane; (R)-Epichlorohydrin	51594-55-9	C₃H₅ClO	详情	详情
(II)	61470	(1S,5R)-1-phenyl-3-oxabicyclo[3.1.0]hexan-2-one	63106-93-4	C₁₁H₁₀O₂	详情	详情
(III)	67285	(1R,2S)-2-(hydroxymethyl)-1-phenylcyclopropanecarbonitrile		C₁₁H₁₁NO	详情	详情
(III)	67290	(1S,2R)-N,N-diethyl-2-(hydroxymethyl)-1-phenylcyclopropanecarboxamide		C₁₅H₂₁NO₂	详情	详情
(IV)	61470	(1S,5R)-1-phenyl-3-oxabicyclo[3.1.0]hexan-2-one	63106-93-4	C₁₁H₁₀O₂	详情	详情
(IV)	67291	(1R,2S)-2-(azidomethyl)-N,N-diethyl-1-phenylcyclopropanecarboxamide		C₁₅H₂₀N₄O	详情	详情
(V)	67287	(1S,2R)-2-((1,3-dioxoisoindolin-2-yl)methyl)-1-phenylcyclopropanecarboxylic acid		C₁₉H₁₅NO₄	详情	详情
(VI)	67286	(1R,2S)-2-((1,3-dioxoisoindolin-2-yl)methyl)-1-phenylcyclopropanecarbonyl chloride		C₁₉H₁₄ClNO₃	详情	详情
(VII)	67288	(1R,2S)-2-((1,3-dioxoisoindolin-2-yl)methyl)-N,N-diethyl-1-phenylcyclopropanecarboxamide		C₂₃H₂₄N₂O₃	详情	详情
(VIII)	67289	(1R,2S)-2-(aminomethyl)-N,N-diethyl-1-phenylcyclopropanecarboxamide	92623-85-3	C₁₅H₂₂N₂O	详情	详情

合成路线3

该中间体在本合成路线中的序号：(II)

参考文献中间体

合成目标

【1】王晓琴，徐鹏，顾君琳，等.2004.盐酸米那普仑右旋异构体的合成。中国医药工业杂志，35（5）：259～260.
【2】 Bonnaud B, Cousse H, Mouzin G, et al. 1987. 1-Aryl-2-(aminomethyl) cyclopropanecarboxylic acid derivatives. A new series of potential antidepressants. J Med Chem, 30: 318～325.

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)	17046	Phenylacetonitrile; 2-phenylacetonitrile; Benzyl cyanide	140-29-4	C₈H₇N	详情	详情
(I)	17046	Phenylacetonitrile; 2-phenylacetonitrile; Benzyl cyanide	140-29-4	C₈H₇N	详情	详情
(II)	38067	(2R)-2-(Chloromethyl)oxirane; (R)-Epichlorohydrin	51594-55-9	C₃H₅ClO	详情	详情
(II)	61470	(1S,5R)-1-phenyl-3-oxabicyclo[3.1.0]hexan-2-one	63106-93-4	C₁₁H₁₀O₂	详情	详情
(III)	67285	(1R,2S)-2-(hydroxymethyl)-1-phenylcyclopropanecarbonitrile		C₁₁H₁₁NO	详情	详情
(III)	67290	(1S,2R)-N,N-diethyl-2-(hydroxymethyl)-1-phenylcyclopropanecarboxamide		C₁₅H₂₁NO₂	详情	详情
(IV)	61470	(1S,5R)-1-phenyl-3-oxabicyclo[3.1.0]hexan-2-one	63106-93-4	C₁₁H₁₀O₂	详情	详情
(IV)	67291	(1R,2S)-2-(azidomethyl)-N,N-diethyl-1-phenylcyclopropanecarboxamide		C₁₅H₂₀N₄O	详情	详情
(V)	67287	(1S,2R)-2-((1,3-dioxoisoindolin-2-yl)methyl)-1-phenylcyclopropanecarboxylic acid		C₁₉H₁₅NO₄	详情	详情
(VI)	67286	(1R,2S)-2-((1,3-dioxoisoindolin-2-yl)methyl)-1-phenylcyclopropanecarbonyl chloride		C₁₉H₁₄ClNO₃	详情	详情
(VII)	67288	(1R,2S)-2-((1,3-dioxoisoindolin-2-yl)methyl)-N,N-diethyl-1-phenylcyclopropanecarboxamide		C₂₃H₂₄N₂O₃	详情	详情
(VIII)	67289	(1R,2S)-2-(aminomethyl)-N,N-diethyl-1-phenylcyclopropanecarboxamide	92623-85-3	C₁₅H₂₂N₂O	详情	详情

合成路线4

该中间体在本合成路线中的序号：(II)

参考文献中间体

合成目标

【1】 Roggen H, Kehler J, Stensbol TB, et al.2007.Synthesis of enantiomerically pure milnacipran analogs and inhibitions of dopamine, serotonin, and norepinephrine transporters. Bioorg Med Chem, 17:2834～2837.

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)	17046	Phenylacetonitrile; 2-phenylacetonitrile; Benzyl cyanide	140-29-4	C₈H₇N	详情	详情
(II)	61470	(1S,5R)-1-phenyl-3-oxabicyclo[3.1.0]hexan-2-one	63106-93-4	C₁₁H₁₀O₂	详情	详情
(III)	67290	(1S,2R)-N,N-diethyl-2-(hydroxymethyl)-1-phenylcyclopropanecarboxamide		C₁₅H₂₁NO₂	详情	详情

合成路线5

该中间体在本合成路线中的序号：(II)

参考文献中间体

合成目标

【1】 Lee IH, Lee JO, Moon BH, et al.2007. Preparation of cis-milnacipran hydrochloride. JP2007023005.

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)	17046	Phenylacetonitrile; 2-phenylacetonitrile; Benzyl cyanide	140-29-4	C₈H₇N	详情	详情
(II)	61470	(1S,5R)-1-phenyl-3-oxabicyclo[3.1.0]hexan-2-one	63106-93-4	C₁₁H₁₀O₂	详情	详情
(III)	67290	(1S,2R)-N,N-diethyl-2-(hydroxymethyl)-1-phenylcyclopropanecarboxamide		C₁₅H₂₁NO₂	详情	详情

合成路线6

该中间体在本合成路线中的序号：(III)

参考文献中间体

合成目标

【1】 Bonnaud B, Cousse H, Mouzin G, et al. 1987. 1-Aryl-2-(aminomethyl) cyclopropanecarboxylic acid derivatives. A new series of potential antidepressants. J Med Chem, 30: 318～325.
【2】 Shi ZH, Ning Q, Zhou WC.2005.Synthesis of trans isomers of milnacipran hydrochloride. Farming Zhuanli Shenqing Gongkai Shoumingshu. CN1699332.

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)	17046	Phenylacetonitrile; 2-phenylacetonitrile; Benzyl cyanide	140-29-4	C₈H₇N	详情	详情
(II)	67292	(1R,2R)-2-(hydroxymethyl)-1-phenylcyclopropanecarboxylic acid		C₁₁H₁₂O₃	详情	详情
(III)	61470	(1S,5R)-1-phenyl-3-oxabicyclo[3.1.0]hexan-2-one	63106-93-4	C₁₁H₁₀O₂	详情	详情
(IV)	67292	(1R,2R)-2-(hydroxymethyl)-1-phenylcyclopropanecarboxylic acid		C₁₁H₁₂O₃	详情	详情
(V)	67293	(1R,2R)-2-(bromomethyl)-1-phenylcyclopropanecarboxylic acid		C₁₁H₁₁BrO₂	详情	详情
(VI)	67294	(1R,2R)-2-(bromomethyl)-N,N-diethyl-1-phenylcyclopropanecarboxamide		C₁₅H₂₀BrNO	详情	详情
(VII)	67295	(1S,2S)-2-((1,3-dioxoisoindolin-2-yl)methyl)-1-phenylcyclopropanecarboxylic acid		C₁₉H₁₅NO₄	详情	详情

合成路线7

该中间体在本合成路线中的序号：(II)

参考文献中间体

合成目标

【1】 Michael P,W WH. 2001. A new enantiselective synthesis of milnacipran and an analogue by catalytic asymmertric cyclopropanation. Adv Synth Catal, 343(5):299～302.

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)	67296	allyl 2-diazo-2-phenylacetate		C₁₁H₁₀N₂O₂	详情	详情
(II)	61470	(1S,5R)-1-phenyl-3-oxabicyclo[3.1.0]hexan-2-one	63106-93-4	C₁₁H₁₀O₂	详情	详情
(III)	67290	(1S,2R)-N,N-diethyl-2-(hydroxymethyl)-1-phenylcyclopropanecarboxamide		C₁₅H₂₁NO₂	详情	详情
(IV)	67291	(1R,2S)-2-(azidomethyl)-N,N-diethyl-1-phenylcyclopropanecarboxamide		C₁₅H₂₀N₄O	详情	详情

Extended Information