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CAS No. : | 155601-65-3 | MDL No. : | MFCD08277633 |
Formula : | C6H3F2NO | Boiling Point : | No data available |
Linear Structure Formula : | - | InChI Key : | ZYCCUPSLEFLBNR-UHFFFAOYSA-N |
M.W : | 143.09 | Pubchem ID : | 10701929 |
Synonyms : |
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Signal Word: | Warning | Class: | |
Precautionary Statements: | P280-P305+P351+P338 | UN#: | |
Hazard Statements: | H302 | Packing Group: | |
GHS Pictogram: |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
6.25 g (82%) | With sodium hydroxide; In 1-methyl-pyrrolidin-2-one; | Part (b) 2,6-Difluoropyridine-3-carboxaldehyde (4.89 g, 0.034 mole) was dissolved in 20 mL of N-methylpyrrolidone and chilled in an ice/water bath. N-methylpiperazine (3.5 g, 0.035 mole) was added dropwise and the reaction mixture was stirred for 15 minutes and then distributed between 5% NaOH and Et2 O. The organic phase was dried and concentrated to give 6.25 g (82%) of product. An analytical sample was obtained by recrystallization from pentane, mp 77-78 C. Analysis: Calculated for C11 H14 FN3 O: 59.18% C; 6.32% H; 18.82% N; Found: 58.97% C; 6.31% H; 18.95% N. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With potassium carbonate; In N,N-dimethyl-formamide; at 100℃; for 2h; | A mixture of <strong>[155601-65-3]2,6-difluoro-pyridine-3-carbaldehyde</strong> (1.10 g, 7.69 mmol), 4-hydroxy- benzoic acid methyl ester (1.17 g, 7.69 mmol) and K2CO3 (0.552 g, 4.00 mmol) in DMF (10 mL) was stirred at 100 0C for 2 h. The mixture was cooled to room temperature and DMF was removed. Aqueous work-up and purification by flash chromatography on silica gel (EtOAc/hexanes, 1 :4 in v/v) followed by recrystallization from EtOAc/hexanes afforded 4-(6- fluoro-5-formyl-pyridin-2-yloxy)-benzoic acid methyl ester as a white solid (1.48 g, 70%). H NMR (CDCl3) 6 3.94 (s, 2H), 6.94 (d, IH, J= 8.4 Hz), 122-126 (m, 2H), 8.12-8.16 (m, 2H), 8.29-8.35 (m, IH), 10.19 (s, IH). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
toluene-4-sulfonic acid; In ethanol;Heating / reflux; | A solution of <strong>[155601-65-3]2,6-difluoronicotinaldehyde</strong> (5 g, 34.94 mmol), triethyl orthoformate (8.72 ml, 52.41 mmol) and p-toluenesulfonic acid (0.562 mL, 3.49 mmol) in ethanol (50 mL) was heated at reflux overnight. Solvent was removed and the residue was diluted with EtOAc and washed with aqueous K2CO3 and brine. Drying (MgSO4) and removal of solvent gave an oil. The oil was distilled under high vacuum conditions bulb-to-bulb to give 2.85 g of product as a clear, colorless oil.1H NMR: 1.25 (t, 3H), 3.5-3.7 (m 2H), 5.6 (s, IH), 6.85 (d, 2H), 8.1 (dd, IH). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | Under N2, to a solution of 2,6-difluoropyridine (4.95 g, 43.0 mmol) in anhydrous THF (100 mL) cooled at- -78C was added LDA (2.0 M in heptane/THF/ethylbenzene, 23.0 mL, 46.0 mmol). After the mixture was stirred at -780C for 30 min 1-formylpiperidine (4.98 g, 44.0 mmol) was added. The mixture was stirred at -78C for 20 min, and at -78C aqueous HCl (3 N, 60 mL) and Et2O (50 mL) were added. The ether layer was collected and the aqueous layer was extracted with Et2O (3 X 100 mL). The combined extracts were dried over anhydrous Na2SO4. After filtration the solvent was removed, and the residue was purified by flash chromatography on silica gel (CH2Cl2/hexanes, 1:1 v/v) to afford 2,6-difluoro-pyridme-3- carbaldehyde as a pale yellow liquid (1.41 g, 60%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | A mixture of <strong>[155601-65-3]2,6-difluoronicotinaldehyde</strong> (2 g, 13.9 mmol), 2-amino-5-methylphenol (1.7 g, 13.8 mmol) and 2,3-butanedione monoxime (1.065 g, 10.5 mnol) in acetic acid (120 mL) was heated at 120 C for 1.5 hours. After cooling down to room temperature, zinc powder (2 g) was added and the mixture heated one hour at 120 C and left overnight at room temperature. The suspension is then filtered and filtrate is reduced to about 20 mL. Water was added (about 100 mL) and aqueous KOH was added up to pH ~ 8. The mixture was extracted with dichloromethane and the crude obtained purified by column chromatography using CH2Cl2/Et2O as eluent. The ligand was obtained as a beige solid (2.14 g, yield 68 %) 1H NMR (CDCl3, 400 MHz): delta 8.28 (t, J= 8.0 Hz, 1H); 7.25 (d, J= 1.6 Hz, 1H); 7.09 (d, J= 8.4 Hz, 1H); 6.99 (ddd, J= 8.0, 2.0, 0.8 Hz, 1H); 6.79 (dd, J= 8.4, 2.8 Hz, 1H); 2.27 (s, 3H); 2.24 (d, J= 0.8 Hz, 3H); 2.19 (d, J= 0.8 Hz, 3H). | |
68% | <strong>[155601-65-3]2,6-difluoronicotinaldehyde</strong> was obtained as described in M. Schlosser and T. Rausis, Eur. J. Org. Chem. 2004, 1018.A mixture of <strong>[155601-65-3]2,6-difluoronicotinaldehyde</strong> (2 g, 13.9 mmol), 2-amino-5- methylphenol (1.7 g, 13.8 mmol) and 2,3-butanedione monoxime (1.065 g, 10.5 mmol) in acetic acid (120 mL) was heated at 120C for 1.5 hours. After cooling down to room temperature, zinc powder (2 g) was added and the mixture heated one hour at 120C and left overnight at room temperature. The suspension is then filtered and filtrate is reduced to about 20 mL. Water was added (about 100 mL) and aqueous KOH was added up to pH ~ 8. The mixture was extracted with dichloromethane and the crude obtained purified by column chromatography using CH2Cl2/Et20 as eluent. The ligand was obtained as a beige solid (2.14 g, yield 68 %).1H MR (CDC13, 400 MHz) : delta 8.28 (t, J= 8.0 Hz, IH) ; 7.25 (d, J= 1.6 Hz, IH) ; 7.09 (d, J= 8.4 Hz, IH) ; 6.99 (ddd, J= 8.0, 2.0, 0.8 Hz, IH) ; 6.79 (dd, J= 8.4, 2.8 Hz, IH) ; 2.27 (s, 3H) ; 2.24 (d, J= 0.8 Hz, 3H) ; 2.19 (d, J= 0.8 Hz, 3H). |