(2R)-6-fluoro-2-[(2R)oxiranyl]-3,4-dihydro-2H-chromene -Drug Synthesis Database

【结构式】

【分子编号】40863

【品名】(2R)-6-fluoro-2-[(2R)oxiranyl]-3,4-dihydro-2H-chromene

【CA登记号】

【分子式】C₁₁H₁₁FO₂

【分子量】194.2055432

【元素组成】C 68.03% H 5.71% F 9.78% O 16.48%

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：(XXI)

The treatment of (XI) under the Sharpless asymmetric epoxidation conditions (but using (+)-DET and titanium tetraisopropoxide) gives, after cyclization with NaOH, 1(S)-(6-fluoro-3,4-dihydro-2H-1-benzopyran-2(R)-yl)-1,2-ethanediol (XVI), which is benzoylated with 4-nitrobenzoic acid (XVII), DEAD and PPh3 yielding the dibenzoate (XVIII), with inversion of the configuration at the OH group. The hydrolysis of (XVIII) with NaOMe in methanol affords, 1(R)-(6-fluoro-3,4-dihydro-2H-1-benzopyran-2(R)-yl)-1,2-ethanediol (XIX), which is selectively tosylated with TsCl and pyridine giving the monotosylate (XX). The cyclization of (XX) with NaOMe furnishes the expected epoxide (XXI), which is finally condensed with the previously described intermediate amine (XV).

参考文献中间体

合成目标

【1】 Chandrasekhar, S.; Reddy, M.V.; Enantioselective total synthesis of the antihypertensive agent (S,R,R,R)-nebivolol. Tetrahedron 2000, 56, 34, 6339.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XI)	40855	4-fluoro-2-[(E)-5-hydroxy-3-pentenyl]phenol		C₁₁H₁₃FO₂	详情	详情
(XV)	40859	(1R)-2-amino-1-[(2S)-6-fluoro-3,4-dihydro-2H-chromen-2-yl]-1-ethanol		C₁₁H₁₄FNO₂	详情	详情
(XVI)	40856	(1R)-1-[(2S)-6-fluoro-3,4-dihydro-2H-chromen-2-yl]-1,2-ethanediol		C₁₁H₁₃FO₃	详情	详情
(XVII)	18119	4-nitrobenzoic acid; p-nitrobenzoic acid	62-23-7	C₇H₅NO₄	详情	详情
(XVIII)	40860	(1R)-1-[(2R)-6-fluoro-3,4-dihydro-2H-chromen-2-yl]-2-[(4-nitrobenzoyl)oxy]ethyl 4-nitrobenzoate		C₂₅H₁₉FN₂O₉	详情	详情
(XIX)	40861	(1R)-1-[(2R)-6-fluoro-3,4-dihydro-2H-chromen-2-yl]-1,2-ethanediol		C₁₁H₁₃FO₃	详情	详情
(XX)	40862	(2R)-2-[(2R)-6-fluoro-3,4-dihydro-2H-chromen-2-yl]-2-hydroxyethyl 4-methylbenzenesulfonate		C₁₈H₁₉FO₅S	详情	详情
(XXI)	40863	(2R)-6-fluoro-2-[(2R)oxiranyl]-3,4-dihydro-2H-chromene		C₁₁H₁₁FO₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VI)

参考文献中间体

合成目标

【1】 Sheth R, Attanti SV, Patel HM, et al.2006.Nebivolol and its pharmaceutically acceptable salts, process for preparation and pharmaceutical compositions of nebivolol. WO 2006025070.

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)	60391	1-(5-fluoro-2-hydroxyphenyl)-1-ethanone	394-32-1	C₈H₇FO₂	详情	详情
(II)	67329	6-fluoro-4-oxo-4H-chromene-2-carboxylic acid, sodium salt		C₁₀H₅FO₄.Na	详情	详情
(III)	19528	6-fluoro-2-chromanecarboxylic acid		C₁₀H₉FO₃	详情	详情
(IV)	67330	(6-fluorochroman-2-yl)(piperidin-1-yl)methanone		C₁₅H₁₈FNO₂	详情	详情
(V)	19529	6-fluoro-2-chromanecarbaldehyde		C₁₀H₉FO₂	详情	详情
(VI)	40863	(2R)-6-fluoro-2-[(2R)oxiranyl]-3,4-dihydro-2H-chromene		C₁₁H₁₁FO₂	详情	详情
(VII)	67317	2-(benzylamino)-1-(6-fluorochroman-2-yl)ethanol		C₁₈H₂₀FNO₂	详情	详情
(VIII)	67318	(S)-1-((R)-6-fluorochroman-2-yl)-2-(((S)-2-((S)-6-fluorochroman-2-yl)-2-hydroxyethyl)(phenyl)amino)ethanol		C₂₈H₂₉F₂NO₄	详情	详情
(XI)	67300	(R)-6-fluoro-2-((R)-oxiran-2-yl)chroman		C₁₁H₁₁FO₂	详情	详情

合成路线3

该中间体在本合成路线中的序号：(XII)

参考文献中间体

合成目标

【1】 Trinka P, Reiter J, Beracz G, et al. 2004. New process for the preparation of racemic ([2S [2R * [R[R]]]]) and ([2R [2S [S[S]]]]) -(+-)-α,α'-[imino-bis (methylene)] bis [6-fluoro-chroman-2-methanol] and its pure [2S [2R [R[R]]]]) -, and [2R [2S [S[S*]]]] enantionmers. WO 2004041805.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
（XV）	67337	(S)-2-((S)-1,2-dihydroxyethyl)-6-fluorochroman-4-one		C₁₁H₁₁FO₄	详情	详情
（X）	67339	(R)-1-((S)-6-fluorochroman-2-yl)-2-(phenylamino)ethanol		C₁₇H₁₈FNO₂	详情	详情
(I)	19639	4-fluorophenol	371-41-5	C₆H₅FO	详情	详情
(II)	67331	2-chloro-1-(5-fluoro-2-hydroxyphenyl)ethanone		C₈H₆ClFO₂	详情	详情
(III)	67332	(2-(5-fluoro-2-hydroxyphenyl)-2-oxoethyl)triphenylphosphonium chloride		C₂₆H₂₁ClFO₂P	详情	详情
(IV)	67333	1-(5-fluoro-2-hydroxyphenyl)-2-(triphenylphosphoranylidene)ethanone		C₂₆H₂₀FO₂P	详情	详情
(V)	67334	(R,E)-3-(2,2-dimethyl-1,3-dioxolan-4-yl)-1-(5-fluoro-2-hydroxyphenyl)prop-2-en-1-one		C₁₄H₁₅FO₄	详情	详情
(VI)	67335	2-(2,2-dimethyl-1,3-dioxolan-4-yl)-6-fluorochroman-4-one		C₁₄H₁₅FO₄	详情	详情
(VII)	67336	(S)-2-((R)-1,2-dihydroxyethyl)-6-fluorochroman-4-one		C₁₁H₁₁FO₄	详情	详情
(VIII)	40857	(2R)-2-[(2S)-6-fluoro-3,4-dihydro-2H-chromen-2-yl]-2-hydroxyethyl 4-methylbenzenesulfonate		C₁₈H₁₉FO₅S	详情	详情
(IX)	67338	(S)-6-fluoro-2-((R)-oxiran-2-yl)chroman		C₁₁H₁₁FO₂	详情	详情
(XI)	40862	(2R)-2-[(2R)-6-fluoro-3,4-dihydro-2H-chromen-2-yl]-2-hydroxyethyl 4-methylbenzenesulfonate		C₁₈H₁₉FO₅S	详情	详情
(XII)	40863	(2R)-6-fluoro-2-[(2R)oxiranyl]-3,4-dihydro-2H-chromene		C₁₁H₁₁FO₂	详情	详情
(XIII)	67318	(S)-1-((R)-6-fluorochroman-2-yl)-2-(((S)-2-((S)-6-fluorochroman-2-yl)-2-hydroxyethyl)(phenyl)amino)ethanol		C₂₈H₂₉F₂NO₄	详情	详情

Extended Information