1-(5-fluoro-2-hydroxyphenyl)-1-ethanone -Drug Synthesis Database

【结构式】

【分子编号】60391

【品名】1-(5-fluoro-2-hydroxyphenyl)-1-ethanone

【CA登记号】394-32-1

【分子式】C₈H₇FO₂

【分子量】154.1407832

【元素组成】C 62.34% H 4.58% F 12.33% O 20.76%

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：(I)

Aldol condensation between 5'-fluoro-2'-hydroxyacetophenone (I) and 4-(methylthio)benzaldehyde (II) produces chalcone (III). Oxidative cyclization of (III) in hot DMSO in the presence of iodine leads to the flavone compound (IV). Further oxidation of the methylthio group of (IV) employing oxone furnishes sulfone (V). Conversion of flavone (V) into the 3-iodo derivative (VI) is carried out by treatment with iodine and bis(trifluoroacetoxy)iodobenzene. Finally, Suzuki coupling of the iodoflavone (VI) with lithium trimethoxy-3-pyridylboronate (VII) provides the desired 2,3-diaryl benzopyranone

参考文献中间体

合成目标

【1】 Joo, Y.H.; Kim, J.K.; Kang, S-H.; Noh, M-S.; Ha, J-Y.; Choi, J.K.; Lim, K.M.; Lee, C.H.; Chung, S.; Diarylbenzopyran derivatives as a selective inhibitor of cyclooxygenase-2. 224th ACS Natl Meet (Aug 18 2002, Boston) 2002, Abst MEDI 313.
【2】 Kim, J.K.; Choi, J.K.; Lee, C.H.; Joo, Y.H.; Noh, M.-S.; Ha, J.-Y.; Lim, K.M.; Kang, S.-H. (Pacific Corp.); Diarylbenzopyran derivs. as cyclooxygenase-2 inhibitors. EP 1105384; JP 2002523410; US 6340694; WO 0010993 .

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)	18815	4-(methylsulfanyl)benzaldehyde; 4-(methylmercapto)benzaldehyde	3446-89-7	C₈H₈OS	详情	详情
(III)	60392	(E)-1-(5-fluoro-2-hydroxyphenyl)-3-[4-(methylsulfanyl)phenyl]-2-propen-1-one		C₁₆H₁₃FO₂S	详情	详情
(IV)	60393	6-fluoro-2-[4-(methylsulfanyl)phenyl]-4H-chromen-4-one		C₁₆H₁₁FO₂S	详情	详情
(V)	60394	6-fluoro-2-[4-(methylsulfonyl)phenyl]-4H-chromen-4-one		C₁₆H₁₁FO₄S	详情	详情
(VI)	60395	6-fluoro-3-iodo-2-[4-(methylsulfonyl)phenyl]-4H-chromen-4-one		C₁₆H₁₀FIO₄S	详情	详情
(VII)	30006	Trimethoxy(3-pyridyl)boranuide lithium salt		C₈H₁₃BLiNO₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(V)

参考文献中间体

合成目标

【1】王乃兴，于安广，王桂霞，等。2007.（R,R,R,S）2,2'-[亚氨基二（亚甲基）]双-（6-氟-3,4-二氢-2H-1-苯骈吡喃-2-甲醇）奈比洛尔盐酸盐的合成方法。发明专利申请公开说明书，1978442.

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)	67319	(2R,3S,4R,5S)-hexane-1,2,3,4,5,6-hexaol	50-70-4	C₆H₁₄O₆	详情	详情
(II)	45944	(1S,2S)-1,2-bis[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-1,2-ethanediol	1707-77-3	C₁₂H₂₂O₆	详情	详情
(III)	36759	(4R)-2,2-dimethyl-1,3-dioxolane-4-carbaldehyde	15186-48-8	C₆H₁₀O₃	详情	详情
(IV)	19639	4-fluorophenol	371-41-5	C₆H₅FO	详情	详情
(V)	60391	1-(5-fluoro-2-hydroxyphenyl)-1-ethanone	394-32-1	C₈H₇FO₂	详情	详情
(VI)	67320	(S)-2-(R-2,2-dimethyl-1,3-dioxolan-4-yl)-6-fluorochroman-4-one		C₁₄H₁₅FO₄	详情	详情
(VII)	67314	(S)-1-((S)-6-fluorochroman-2-yl)ethane-1,2-diol		C₁₁H₁₃FO₃	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)	67305	(S)-2-amino-1-((S)-6-fluorochroman-2-yl)ethanol		C₁₁H₁₄FNO₂	详情	详情
(XI)	67321	(R)-2-(R-2,2-dimethyl-1,3-dioxolan-4-yl)-6-fluorochroman-4-one		C₁₄H₁₅FO₄	详情	详情
(XII)	67313	(S)-1-((R)-6-fluorochroman-2-yl)ethane-1,2-diol		C₁₁H₁₃FO₃	详情	详情
(XIII)	67315	(S)-2-((R)-6-fluorochroman-2-yl)-2-hydroxyethyl 4-methylbenzenesulfonate		C₁₈H₁₉FO₅S	详情	详情

合成路线3

该中间体在本合成路线中的序号：(I)

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

Extended Information