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【结 构 式】 
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【分子编号】47247 【品名】3-Furaldehyde 【CA登记号】498-60-2 |
【 分 子 式 】C5H4O2 【 分 子 量 】96.08556 【元素组成】C 62.5% H 4.2% O 33.3% |
合成路线1
该中间体在本合成路线中的序号：(I)Reaction of 3-furancarboxaldehyde (I) with potassium cyanide in the presence of tert-butyldimethylsilyl chloride and ZnI2 gave the O-silylated cyanohydrin (II). Addition of 2(5H)-furanone (III) to the lithium anion of (II), followed by addition of 3,4-dimethoxybenzaldehyde (V) to the intermediate (IV), yielded adduct (VI). Subsequent acid cyclization of (VI) by means of trifluoroacetic acid or methanesulfonic acid provided the tricyclic derivative (VII) as a diastereomeric mixture. Desilylation of (VII) with concomitant cyanide elimination using either tetrabutylammonium fluoride at low temperature or aqueous ammonium fluoride gave rise to ketone (VIII). This was then epimerized to the title compound by treatment with triethylamine in boiling toluene. Alternatively, desilylation of (VII) with tetrabutylammonium fluoride at room temperature provided directly the title diastereoisomer.
| 【1】 Iwasaki, T.; Sugiura, M.; Matsuoka, Y.; Matsumoto, M.; Kitamura, K. (Tanabe Seiyaku Co., Ltd.); Biphenyl derivs.. EP 0386778; JP 1990235884; US 5066669 . |
| 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) | 47248 | 2-[[tert-butyl(dimethyl)silyl]oxy]-2-(3-furyl)acetonitrile | C12H19NO2Si | 详情 | 详情 | |
| (III) | 19267 | 2(5H)-furanone；furan-2(5H)-one；2-Buten-1,4-olide | 497-23-4 | C4H4O2 | 详情 | 详情 |
| (IV) | 47249 | C16H22LiNO4Si | 详情 | 详情 | ||
| (V) | 18304 | 3,4-Dimethoxybenzaldehyde; Veratraldehyde | 120-14-9 | C9H10O3 | 详情 | 详情 |
| (VI) | 47250 | 2-[[tert-butyl(dimethyl)silyl]oxy]-2-[4-[(3,4-dimethoxyphenyl)(hydroxy)methyl]-5-oxotetrahydro-3-furanyl]-2-(3-furyl)acetonitrile | C25H33NO7Si | 详情 | 详情 | |
| (VII) | 47251 | (4S,4aR,7aR,8R)-4-[[tert-butyl(dimethyl)silyl]oxy]-8-(3,4-dimethoxyphenyl)-7-oxo-4,4a,5,7,7a,8-hexahydrofuro[2,3-f][2]benzofuran-4-carbonitrile | C25H31NO6Si | 详情 | 详情 | |
| (VIII) | 47252 | (4R,4aR,7aR,8R)-4-[[tert-butyl(dimethyl)silyl]oxy]-8-(3,4-dimethoxyphenyl)-7-oxo-4,4a,5,7,7a,8-hexahydrofuro[2,3-f][2]benzofuran-4-carbonitrile | C25H31NO6Si | 详情 | 详情 | |
| (IX) | 47253 | (4aR,7aR,8R)-8-(3,4-dimethoxyphenyl)-4a,5,7a,8-tetrahydrofuro[2,3-f][2]benzofuran-4,7-dione | C18H16O6 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(I)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.
| 【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3
该中间体在本合成路线中的序号：(I)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.
| 【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 |
合成路线4
该中间体在本合成路线中的序号：(II)The title compound is prepared by condensation between 5-fluoro-2-methylindene-3-acetic acid (I) and 3-furaldehyde (II) in the presence of NaOMe.
