| Identification | Back Directory | [Name]
5-1-hydroxy-2-(2,4,5-trifluorophenyl)ethylidene-2,2-dimethyl-1,3-dioxane-4,6-dione | [CAS]
764667-64-3 | [Synonyms]
ethylidene)
Sitagliptin-9
Sitagliptin Impurity 96
5-(1-Hydroxy-2-(2,4,5-trifluorophenyl)
5-[1-hydroxy-2-92,4,5-trifluorophenyl0ethylidene]-2,2-dimethyl
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
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
Sitagliptin impurity 42/Sitagliptin Dioxo Impurity/5-(1-hydroxy-2-(2,4,5-trifluorophenyl)ethylidene)-2,2-dimethyl- 1,3-dioxane-4,6-dione | [Molecular Formula]
C14H11F3O5 | [MDL Number]
MFCD12407134 | [MOL File]
764667-64-3.mol | [Molecular Weight]
316.23 |
| Chemical Properties | Back Directory | [Melting point ]
117 °C (decomp) | [Boiling point ]
489.0±45.0 °C(Predicted) | [density ]
1.462±0.06 g/cm3(Predicted) | [storage temp. ]
Inert atmosphere,2-8°C | [solubility ]
Chloroform (Slightly), Ethyl Acetate (Slightly), Methanol (Slightly) | [form ]
Solid | [pka]
4.50±1.00(Predicted) | [color ]
White to Off-White |
| Hazard Information | Back Directory | [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 |
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