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CAS No. : | 58481-11-1 | MDL No. : | MFCD01765409 |
Formula : | C7H6ClNO2 | Boiling Point : | No data available |
Linear Structure Formula : | - | InChI Key : | KKOUHTMLFUAAGG-UHFFFAOYSA-N |
M.W : | 171.58 | Pubchem ID : | 2736842 |
Synonyms : |
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Signal Word: | Warning | Class: | |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | |
Hazard Statements: | H315-H319-H335 | 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 |
---|---|---|
With sodium hydride; In 1,2-dimethoxyethane; at 95℃; | Example 18; A. 3-[2-(2-chloropyridin-4-yl)-2-oxoethyl]isonicotinonitrile and 3-[2-(2-methoxypyridin- 4-yl)-2-oxoethyl]isonicotinonitrile.; In a three-necked round-bottomed flask equipped with a reflux cooler, 60 % NaH in mineral oil (1.35 g, 33.9 mmol) is added to DME (70 ml_). The suspension is heated to 95 0C and a solution of <strong>[7584-05-6]3-methylisonicotinonitrile</strong> (1.00 g, 8.47 mmol) and 2-chloroisonicotinic acid methyl ester (2.18 g, 12.71 mmol) in DME (15 mL) is added. The resulting reaction mixture is stirred overnight at 95 0C. After cooling down to room temperature the reaction mixture is partitioned between EtOAc and water. The aqueous phase is extracted with EtOAc and the combined organic layers are dried over Na2SO4, filtered and concentrated in vacuo to afford <n="182"/>a 1 : 2 mixture of 3-[2-(2-chloropyridin-4-yl)-2-oxoethyl]isonicotinonitrile and 3-[2-(2- methoxypyridin-4-yl)-2-oxoethyl]isonicotinonitrile as a brown solid (2.25 g, 8.47 mmol, 100%). 3-[2-(2-chloropyridin-4-yl)-2-oxoethyl]isonicotinonitrile: MS (ES+): 258 (M(C13H8CIN3OHH)+; 3-[2-(2-methoxy-pyridin-4-yl)-2-oxo-ethyl]-isonicotinonitrile: MS (ES+): 254 (M(C14H11N3O2HH)+ . | |
With sodium hydride; In 1,2-dimethoxyethane; at 95℃; | 3-[2-(2-chloro-pyridin-4-yl)-2-oxo-ethyl]-isonicotinonitrile and 3-[2-(2-methoxy-pyridin-4-yl)-2- oxo-ethyl]-isonicotinonitrile; In a three-necked round-bottomed flask equipped with a reflux cooler, 60 % NaH in mineral oil (1.35 g, 33.9 mmol) is added to DME (70 ml_). The suspension is heated to 95 0C and a solution of <strong>[7584-05-6]3-methyl-isonicotinonitrile</strong> (1.00 g, 8.47 mmol) and 2-chloro-isonicotinic acid methyl ester (2.18 g, 12.71 mmol) in DME (15 ml_) is added. The resulting reaction mixture is stirred overnight at 95 0C. After cooling down to room temperature the reaction mixture is partitioned between EtOAc and water. The aqueous phase is extracted with EtOAc and the combined organic layers are dried over Na2SO4, filtered and concentrated in vacuo to afford a 1 : 2 mixture of 3-[2-(2-chloro-pyridin-4-yl)-2-oxo-ethyl]-isonicotinonitrile and 3-[2-(2- methoxy-pyridin-4-yl)-2-oxo-ethyl]-isonicotinonitrile as a brown solid (2.25 g, 8.47 mmol, 100%). 3-[2-(2-chloro-pyridin-4-yl)-2-oxo-ethyl]-isonicotinonitrile: MS (ES+): 258 (M(C13H8CIN3O)H-H)+; 3-[2-(2-methoxy-pyridin-4-yl)-2-oxo-ethyl]-isonicotinonitrile: MS (ES+): 254 (M(C14H11N3O2)H-H)+ . |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Zinc powder (1.43 g, 21.87 mmol) was added to a dried flask and was heated at 70 C. under vacuum for 30 minutes. Dry DMA (29 mL) and iodine (0.092 g, 0.37 mmol) were added and the mixture was heated at 70 C. until the red-brown colour had disappeared (approx. 5 minutes). 4-(Bromomethyl)-1,1-difluorocyclohexane (3.1 g, 14.55 mmol) was added and heating was continued for ca. 42 h. The resulting solution was used in the next transformation. To methyl-2-chloroisonicotinate (1.664 g, 9.7 mmol) and bis(tri-tert-butylphosphine)palladium(0) (198 mg, 0.38 mmol) under nitrogen was added tetrahydrofuran (10 mL). To the resulting solution was added freshly prepared ((4,4-difluorocyclohexyl)methyl)zinc(II) bromide (14.55 mmol, 0.5 M in 29 mL DMA) and the resulting brown mixture heated to 60 C. for 4 h. The reaction mixture was diluted with ethyl acetate and washed with satd NaHCO3 (2 times), satd NH4Cl and brine. The organic layer was dried over MgSO4, filtered and evaporated. The residue was dissolved in DCM and added onto an SCX-2 cation exchange column. The column was washed with DCM, MeOH and then eluted with NH3/MeOH. The NH3/MeOH layer was evaporated leaving methyl 2-((4,4-difluorocyclohexyl)methyl)isonicotinate (2 g, 67%) as a yellow oil. 1H NMR (400 MHz, cdcl3) delta 1.30-1.46 (m, 2H), 1.58-1.79 (m, 4H), 1.87-2.14 (m, 3H), 2.82 (d, 2H), 3.96 (s, 3H), 7.65-7.73 (m, 2H), 8.70 (d, 1H). MS m/z 270 (M+H)+ |
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