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【结 构 式】 
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【分子编号】17890 【品名】3-(trifluoromethyl)benzoic acid; m-Trifluoromethylbenzoic acid 【CA登记号】454-92-2 |
【 分 子 式 】C8H5F3O2 【 分 子 量 】190.1217096 【元素组成】C 50.54% H 2.65% F 29.98% O 16.83% |
合成路线1
该中间体在本合成路线中的序号：(I)The reacion of 3-(trifluoromethyl) benzoic acid (I) first with SOCl2 (or oxalyl chloride) and then with NH4OH in dioxane given the corresponding amide (II), which is treated with SOCl2 giving 3-(trifluoromethyl)benzonitrile (III) was condensed with ethylmagnesium bromide to afford ketone (IV), which was brominated in either methanol or dioxane to yield bromoketone (V). Alkylation of tert-butylamine (VI) with bromoketone (V) provided the aminoketone (VII). Reduction of this ketone to the aminoalcohol was performed with several reagents, among them, borane in THF afforded the most favourable ratio for the desired treo diastereoisomer (80:20). Finally, the diastereomeric mixture was separated by preparative HPLC.
| 【1】 Musso, D.L.; et al.; Synthesis and evaluation of the anticonvulsant activity of a series of 2-amino-1-phenyl-1-propanols derived from the metabolites of the antidepressant bupropion. Bioorg Med Chem Lett 1997, 7, 1, 1. |
| 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) | 17890 | 3-(trifluoromethyl)benzoic acid; m-Trifluoromethylbenzoic acid | 454-92-2 | C8H5F3O2 | 详情 | 详情 |
| (II) | 17891 | 3-(trifluoromethyl)benzamide | 1801-10-1 | C8H6F3NO | 详情 | 详情 |
| (III) | 17892 | 3-(trifluoromethyl)benzonitrile; alpha,alpha,alpha-Trifluoro-m-tolunitrile | 368-77-4 | C8H4F3N | 详情 | 详情 |
| (IV) | 17893 | 3-(Trifluoromethyl)propiophenone; 1-[3-(trifluoromethyl)phenyl]-1-propanone | 1533-03-5 | C10H9F3O | 详情 | 详情 |
| (V) | 17894 | 2-bromo-1-[3-(trifluoromethyl)phenyl]-1-propanone | C10H8BrF3O | 详情 | 详情 | |
| (VI) | 17895 | 2-Amino-2-methylpropane; tert-butylamine; 2-methyl-2-propanamine | 75-64-9 | C4H11N | 详情 | 详情 |
| (VII) | 17896 | 2-(tert-butylamino)-1-[3-(trifluoromethyl)phenyl]-1-propanone | C14H18F3NO | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(III)The compound was obtained by solid-phase synthesis on an aminoethyl-photolinker AM resin. Deprotection of hydroxyl and amino groups from disaccharide-resin (I) by means of hydrazine provided (II). Reaction of the resulting free C-2' amino group of (II) with 3-(trifluoromethyl)benzoic acid (III) in the presence of HATU afforded the corresponding amide (IV). Reacetylation of (IV) with acetic anhydride and dimethylaminopyridine gave triacetate (V). Subsequent reduction of the azido group of (V) by means of trimethyl phosphine provided the C-3 amine (VI), which was condensed with 4-chloro-3-(trifluoromethyl)phenyl isocyanate (VII) yielding urea (VIII).
| 【1】 Allanson, N.; Sofia, M.J.; Hatzenbuhler, N.T.; et al.; Discovery of novel disaccharide antibacterial agents using a combinatorial library approach. J Med Chem 1999, 42, 17, 3193. |
| 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) | 37863 | (2R,3R,4R,5R,6S)-3-(acetoxy)-2-[(acetoxy)methyl]-6-[[(2S,3R,4S,5S,6S)-6-(aminocarbonyl)-4-azido-5-methoxy-2-(phenylsulfanyl)tetrahydro-2H-pyran-3-yl]oxy]-5-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)tetrahydro-2H-pyran-4-yl acetate | C33H35N5O13S | 详情 | 详情 | |
| (II) | 37864 | (2S,3S,4S,5R,6S)-5-[[(2S,3R,4R,5S,6R)-3-amino-4,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl]oxy]-4-azido-3-methoxy-6-(phenylsulfanyl)tetrahydro-2H-pyran-2-carboxamide | C19H27N5O8S | 详情 | 详情 | |
| (III) | 17890 | 3-(trifluoromethyl)benzoic acid; m-Trifluoromethylbenzoic acid | 454-92-2 | C8H5F3O2 | 详情 | 详情 |
| (IV) | 37865 | (2S,3S,4S,5R,6S)-4-azido-5-[((2S,3R,4R,5S,6R)-4,5-dihydroxy-6-(hydroxymethyl)-3-[[3-(trifluoromethyl)benzoyl]amino]tetrahydro-2H-pyran-2-yl)oxy]-3-methoxy-6-(phenylsulfanyl)tetrahydro-2H-pyran-2-carboxamide | C27H30F3N5O9S | 详情 | 详情 | |
| (V) | 37866 | (2R,3R,4R,5R,6S)-3-(acetoxy)-2-[(acetoxy)methyl]-6-[[(2S,3R,4S,5S,6S)-6-(aminocarbonyl)-4-azido-5-methoxy-2-(phenylsulfanyl)tetrahydro-2H-pyran-3-yl]oxy]-5-[[3-(trifluoromethyl)benzoyl]amino]tetrahydro-2H-pyran-4-yl acetate | C33H36F3N5O12S | 详情 | 详情 | |
| (VI) | 37867 | (2R,3R,4R,5R,6S)-3-(acetoxy)-2-[(acetoxy)methyl]-6-[[(2S,3R,4S,5S,6S)-4-amino-6-(aminocarbonyl)-5-methoxy-2-(phenylsulfanyl)tetrahydro-2H-pyran-3-yl]oxy]-5-[[3-(trifluoromethyl)benzoyl]amino]tetrahydro-2H-pyran-4-yl acetate | C33H38F3N3O12S | 详情 | 详情 | |
| (VII) | 37868 | 1-chloro-4-isocyanato-2-(trifluoromethyl)benzene; 4-chloro-3-(trifluoromethyl)phenyl isocyanate | 327-78-6 | C8H3ClF3NO | 详情 | 详情 |
| (VIII) | 37869 | C41H41ClF6N4O13S | 详情 | 详情 |