3-methylene-2,3-dihydrofuran -Drug Synthesis Database

【结构式】

【分子编号】55641

【品名】3-methylene-2,3-dihydrofuran

【CA登记号】

【分子式】C₅H₆O

【分子量】82.10204

【元素组成】C 73.15% H 7.37% O 19.49%

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)

A new enantioselective synthesis of (S)-fluoxetine has been reported: Reduction of 3-furaldehyde (I) under Wolff-Kishner conditions provided the desired 3-methylene-2,3-dihydrofuran (II) along with minor amounts of 3-methylfuran (III), which were used in the next step without previous separation. The asymmetric carbonyl-ene reaction of (II) with benzaldehyde (IV) using (S)-1,1'-binaphthol and titanium isopropoxide furnished the target (S)-2-(3-furyl)-1-phenylethanol (V). Condensation of the sodium alkoxide of (V) with 4-fluorobenzotrifluoride (VI) gave rise to ether (VII). Carboxylic acid (VIII) was then obtained by oxidative cleavage of the furan derivative (VII) with RuCl3/NaIO4. Coupling of acid (VIII) with methylamine gave amide (IX). Finally, amide reduction employing borane in THF yielded the title compound.

参考文献中间体

合成目标

【1】 Miles, W.H.; et al.; Enantioselective synthesis of (S)- and (R)-fluoxetine hydrochloride. Tetrahedron 2001, 57, 50, 9925.

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)	47247	3-Furaldehyde	498-60-2	C₅H₄O₂	详情	详情
(II)	55641	3-methylene-2,3-dihydrofuran		C₅H₆O	详情	详情
(III)	55642	3-Methylfuran	930-27-8	C₅H₆O	详情	详情
(IV)	10498	Benzaldehyde;Benzoic aldehyde;Phenylmethanal	100-52-7	C₇H₆O	详情	详情
(V)	55651	(1S)-2-(3-furyl)-1-phenyl-1-ethanol		C₁₂H₁₂O₂	详情	详情
(VI)	52131	4-Fluorobenzotrifluoride; alpha,alpha-4-Tetrafluorotoluene	402-44-8	C₇H₄F₄	详情	详情
(VII)	55652	(1S)-2-(3-furyl)-1-phenylethyl 4-(trifluoromethyl)phenyl ether; 3-{(2S)-2-phenyl-2-[4-(trifluoromethyl)phenoxy]ethyl}furan		C₁₉H₁₅F₃O₂	详情	详情
(VIII)	55653	(3S)-3-phenyl-3-[4-(trifluoromethyl)phenoxy]propanoic acid		C₁₆H₁₃F₃O₃	详情	详情
(IX)	55654	(3S)-N-methyl-3-phenyl-3-[4-(trifluoromethyl)phenoxy]propanamide		C₁₇H₁₆F₃NO₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

Reduction of 3-furaldehyde (I) under Wolff-Kishner conditions provided the desired 3-methylene-2,3-dihydrofuran (II) along with minor amounts of 3-methylfuran (III), which were used in the next step without previous separation. The asymmetric carbonyl-ene reaction of (II) with benzaldehyde (IV) using (R)-1,1'-binaphthol and titanium isopropoxide furnished the target (R)-2-(3-furyl)-1-phenylethanol (V). Condensation of the sodium alkoxide of (V) with 4-fluorobenzotrifluoride (VI) gave rise to ether (VII). Carboxylic acid (VIII) was then obtained by oxidative cleavage of the furan derivative (VII) with RuCl3/NaIO4. Coupling of acid (VIII) with methylamine gave amide (IX). Finally, amide reduction employing borane in THF yielded the title compound.

参考文献中间体

合成目标

【1】 Miles, W.H.; et al.; Enantioselective synthesis of (S)- and (R)-fluoxetine hydrochloride. Tetrahedron 2001, 57, 50, 9925.

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)	47247	3-Furaldehyde	498-60-2	C₅H₄O₂	详情	详情
(II)	55641	3-methylene-2,3-dihydrofuran		C₅H₆O	详情	详情
(III)	55642	3-Methylfuran	930-27-8	C₅H₆O	详情	详情
(IV)	10498	Benzaldehyde;Benzoic aldehyde;Phenylmethanal	100-52-7	C₇H₆O	详情	详情
(V)	55643	(1R)-2-(3-furyl)-1-phenyl-1-ethanol		C₁₂H₁₂O₂	详情	详情
(VI)	52131	4-Fluorobenzotrifluoride; alpha,alpha-4-Tetrafluorotoluene	402-44-8	C₇H₄F₄	详情	详情
(VII)	55644	(1R)-2-(3-furyl)-1-phenylethyl 4-(trifluoromethyl)phenyl ether; 3-{(2R)-2-phenyl-2-[4-(trifluoromethyl)phenoxy]ethyl}furan		C₁₉H₁₅F₃O₂	详情	详情
(VIII)	55645	(3R)-3-phenyl-3-[4-(trifluoromethyl)phenoxy]propanoic acid		C₁₆H₁₃F₃O₃	详情	详情
(IX)	55646	(3R)-N-methyl-3-phenyl-3-[4-(trifluoromethyl)phenoxy]propanamide		C₁₇H₁₆F₃NO₂	详情	详情

Extended Information