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| | 5-1-hydroxy-2-(2,4,5-trifluorophenyl)ethylidene-2,2-dimethyl-1,3-dioxane-4,6-dione Basic information |
| Product Name: | 5-1-hydroxy-2-(2,4,5-trifluorophenyl)ethylidene-2,2-dimethyl-1,3-dioxane-4,6-dione | | Synonyms: | 5-1-hydroxy-2-(2,4,5-trifluorophenyl)ethylidene-2,2-dimethyl-1,3-dioxane-4,6-dione;5-[1-Hydroxy-2-(2,4,5-trifluorophenyl)ethylidene]-2,2-diMethyl-1,3-dioxane-4,6-dion;5-[1-hydroxy-2-92,4,5-trifluorophenyl0ethylidene]-2,2-dimethyl;1,3-Dioxane-4,6-dione,5-[1-hydroxy-2-(2,4,5-trifluorophenyl)ethylidene]-2,2-diMethyl-;5-[1-Hydroxy-2-(2,4,5-trifluorophenyl)-4,6-dionethylidene]-2,2-dimethyl-1,3-dioxane-4,6-dione;5-(1-Hydroxy-2-(2,4,5-trifluorophenyl);ethylidene);Sitagliptin Impurity 96 | | CAS: | 764667-64-3 | | MF: | C14H11F3O5 | | MW: | 316.23 | | EINECS: | | | Product Categories: | Aromatics;Heterocycles;Impurities;Intermediates | | Mol File: | 764667-64-3.mol |  |
| | 5-1-hydroxy-2-(2,4,5-trifluorophenyl)ethylidene-2,2-dimethyl-1,3-dioxane-4,6-dione Chemical Properties |
| Melting point | 117 °C (decomp) | | Boiling point | 489.0±45.0 °C(Predicted) | | density | 1.462±0.06 g/cm3(Predicted) | | storage temp. | under inert gas (nitrogen or Argon) at 2-8°C | | solubility | Chloroform (Slightly), Ethyl Acetate (Slightly), Methanol (Slightly) | | form | Solid | | pka | 4.50±1.00(Predicted) | | color | White to Off-White |
| | 5-1-hydroxy-2-(2,4,5-trifluorophenyl)ethylidene-2,2-dimethyl-1,3-dioxane-4,6-dione Usage And Synthesis |
| Chemical Properties | White to Off-white Solid. | | Uses | 5-[1-Hydroxy-2-(2,4,5-trifluorophenyl)ethylidene]-2,2-dimethyl-1,3-dioxane-4,6-dione is an impurity of the DPP-IV inhibitor Sitagliptin (S491000). | | Application | 5-[1-Hydroxy-2-(2,4,5-trifluorophenyl)ethylidene] is an intermediate for the synthesis of sitagliptin. Sitagliptin is a new type of anti-type II diabetes drug approved by the FDA and the first dipeptidyl peptidase-IV inhibitor drug for the treatment of type II diabetes. | | Synthesis | The general procedure for the synthesis of 5-[1-hydroxy-2-(2,4,5-trifluorophenyl)ethylidene]-2,2-dimethyl-1,3-dioxane-4,6-dione from cyclo(isopropylidene)malonate (Meldrum acid) and 2,4,5-trifluorophenylacetic acid is as follows: in a 1000 mL three-necked flask, sequentially add 2,4,5-trifluorophenylacetic acid (25 g , 0.132 mol), Meldrum acid (21 g, 0.145 mol) and 4-dimethylaminopyridine (DMAP, 1.29 g, 0.0011 mol). Acetonitrile (75 mL) was added as a solvent in a single addition at room temperature. Subsequently, N,N-diisopropylethylamine (49.2 mL, 0.283 mol) was added as a one-time addition while keeping the reaction temperature below 40 °C. Next, pivaloyl chloride (17.8 mL, 0.145 mol) was slowly added dropwise over a period of 1 to 2 hours and the temperature was controlled to not exceed 40 °C. After the dropwise addition, the reaction mixture was stirred at 45-50 °C for 2-3 hours and then cooled to 0 °C. Over a period of 1 hour, 1N HCl (300 mL) was added slowly and dropwise to induce crystallization of the Meldrum acid adduct. The product was collected by filtration and washed with 20% aqueous acetonitrile. After drying, 36.5 g of Meldrum acid adduct was obtained in 88% yield. The structure of the product was confirmed by 1H-NMR (400 MHz, CDCl3) and 13C-NMR (100 MHz, CDCl3). | | References | [1] Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 9, p. 2622 - 2628
[2] Journal of the American Chemical Society, 2004, vol. 126, # 40, p. 13002 - 13009
[3] Journal of the American Chemical Society, 2009, vol. 131, # 25, p. 8798 - 8804
[4] Patent: WO2004/83212, 2004, A1. Location in patent: Page 11-12
[5] Patent: CN107501112, 2017, A. Location in patent: Paragraph 0061; 0062; 0063; 0064 |
| | 5-1-hydroxy-2-(2,4,5-trifluorophenyl)ethylidene-2,2-dimethyl-1,3-dioxane-4,6-dione Preparation Products And Raw materials |
| Raw materials | 2,2-Dimethyl-1,3-dioxane-4,6-dione-->2,4,5-Trifluorophenylacetic acid-->4-Dimethylaminopyridine-->N,N-Diisopropylethylamine-->Pivaloyl chloride-->Hydrochloric acid | | Preparation Products | Methyl 3-Oxo-4-(2,4,5-trifluorophenyl)butanoate-->(Z)-Methyl 3-aMino-4-(2,4,5-trifluorophenyl)but-2-enoate-->Benzenebutanoicacid,b-aMino-2,4,5-trifluoro-,Methylester,(bR)- |
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