N-[(E)-[4-(benzyloxy)phenyl]methylidene]-4-fluoroaniline; N-[(E)-[4-(benzyloxy)phenyl]methylidene]-N-(4-fluorophenyl)amine -Drug Synthesis Database

【结构式】

【分子编号】20651

【品名】N-[(E)-[4-(benzyloxy)phenyl]methylidene]-4-fluoroaniline; N-[(E)-[4-(benzyloxy)phenyl]methylidene]-N-(4-fluorophenyl)amine

【CA登记号】

【分子式】C₂₀H₁₆FNO

【分子量】305.3515832

【元素组成】C 78.67% H 5.28% F 6.22% N 4.59% O 5.24%

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)

Treatment of acid chloride (I) with tributylamine generated the corresponding ketene, which was cyclocondensed to imine (II) to produce the racemic trans b-lactam (III). Resolution of (III) into enantiomers was then achieved by preparative HPLC on a Chiralcel OD column. Subsequent saponification of the desired enantiomer with methanolic LiOH afforded acid (IV), which was converted to acid chloride (V) upon treatment with oxalyl chloride. Further Pd-mediated coupling of (V) with the arylzinc reagent (VI) provided ketone (VII). Then, carbonyl reduction with BH3-Me2S, followed by chromatographic separation of the isomers furnished alcohol (VIII), which was finally deprotected by hydrogenolysis over Pd/C to afford the target phenol.

参考文献中间体

合成目标

【1】 Afonso, A.; Davis, H.R. Jr.; Huynh, T.; Yumibe, N.; Clader, J.W.; Burnett, D.A.; Rosenblum, S.B.; Discovery of 1-(4-fluorophenyl)-(3R)-[3-(4-fluorophenyl)-(3S)-hydroxypropyl]-(4S)-(4-hydroxyphenyl)-2-azetidinone (SCH 58235): A designed, potent, orally active inhibitor of cholesterol absorption. J Med Chem 1998, 41, 6, 973.

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)	20650	methyl 5-chloro-5-oxopentanoate; methyl-4-chloroformylbutyrate	1501-26-4	C₆H₉ClO₃	详情	详情
(II)	20651	N-[(E)-[4-(benzyloxy)phenyl]methylidene]-4-fluoroaniline; N-[(E)-[4-(benzyloxy)phenyl]methylidene]-N-(4-fluorophenyl)amine		C₂₀H₁₆FNO	详情	详情
(III)	20652	(rac)-methyl 3-[(2S,3R)-2-[4-(benzyloxy)phenyl]-1-(4-fluorophenyl)-4-oxoazetidinyl]propanoate		C₂₆H₂₄FNO₄	详情	详情
(IV)	20653	3-[(2S,3R)-2-[4-(benzyloxy)phenyl]-1-(4-fluorophenyl)-4-oxoazetidinyl]propionic acid		C₂₅H₂₂FNO₄	详情	详情
(V)	20654	3-[(2S,3R)-2-[4-(benzyloxy)phenyl]-1-(4-fluorophenyl)-4-oxoazetidinyl]propanoyl chloride		C₂₅H₂₁ClFNO₃	详情	详情
(VI)	20655	bromo(4-fluorophenyl)zinc		C₆H₄BrFZn	详情	详情
(VII)	20656	(3R,4S)-4-[4-(benzyloxy)phenyl]-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3-oxopropyl]-2-azetidinone		C₃₁H₂₅F₂NO₃	详情	详情
(VIII)	20657	(3R,4S)-4-[4-(benzyloxy)phenyl]-1-(4-fluorophenyl)-3-[(3S)-3-(4-fluorophenyl)-3-hydroxypropyl]-2-azetidinone		C₃₁H₂₇F₂NO₃	详情	详情

合成路线2

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】 Wu GZ. Chen X，Wong YS et al.1999.3-hydroxy gamma-lactone based enaptiolelective synthesis of azetidinones. US 5886171

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)	20651	N-[(E)-[4-(benzyloxy)phenyl]methylidene]-4-fluoroaniline; N-[(E)-[4-(benzyloxy)phenyl]methylidene]-N-(4-fluorophenyl)amine		C₂₀H₁₆FNO	详情	详情
(II)	37681	(4S)-4-hydroxydihydro-2(3H)-furanone; (S)-3-Hydroxy-gamma-butyrolactone	7331-52-4	C₄H₆O₃	详情	详情
(III)	20653	3-[(2S,3R)-2-[4-(benzyloxy)phenyl]-1-(4-fluorophenyl)-4-oxoazetidinyl]propionic acid		C₂₅H₂₂FNO₄	详情	详情
(IV)	37683	(2S,3S)-2-[4-(benzyloxy)phenyl]-1-(4-fluorophenyl)-4-oxo-3-azetidinecarbaldehyde		C₂₃H₁₈FNO₃	详情	详情
(V)	37685	[[1-(4-fluorophenyl)vinyl]oxy](trimethyl)silane; 1-(4-fluorophenyl)vinyl trimethylsilyl ether		C₁₁H₁₅FOSi	详情	详情
(VI)	20656	(3R,4S)-4-[4-(benzyloxy)phenyl]-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3-oxopropyl]-2-azetidinone		C₃₁H₂₅F₂NO₃	详情	详情
(VII)	37688	(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3-oxopropyl]-4-(4-hydroxyphenyl)-2-azetidinone		C₂₄H₁₉F₂NO₃	详情	详情
(VIII)	20631	(R)-Methyl oxazaborolidine; (3aR)-1-methyl-3,3-diphenyltetrahydro-3H-pyrrolo[1,2-c][1,3,2]oxazaborole	112022-83-0	C₁₈H₂₀BNO	详情	详情

Extended Information