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CAS No. : | 850142-73-3 | MDL No. : | MFCD04112568 |
Formula : | C6H5BrFNO | Boiling Point : | No data available |
Linear Structure Formula : | - | InChI Key : | SJOBMIWECHDGAY-UHFFFAOYSA-N |
M.W : | 206.01 | Pubchem ID : | 46863893 |
Synonyms : |
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Signal Word: | Warning | Class: | |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | |
Hazard Statements: | H302-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 |
---|---|---|
74% | With potassium carbonate; In acetone;Reflux; | To a stirring solution of 6-bromo-2-fluoropyridin-3-ol (8.80 g, 45.8 mmol) in acetone (150 mL), potassium carbonate (12.67 g, 91.67 mmol) and iodomethane (5.71 mL, 91.7 mmol) were added. The resulting mixture was stirred under reflux overnight. The contents were filtered and the solvent removed in vacuo to give a residue which was purified by automated normal-phase chromatography (0-30% EtOAc/heptane) to give 6-bromo-2-fluoro-3-methoxypyridine (7.00 g, 34.0 mmol, 74% yield) as a white solid. MS (ES+) m/z 206.0 [M+H]+. XH NMR (400 MHz, CDCI3) δ ppm 7.27 - 7.34 (m, 1H), 7.20 (dd, 1H), 3.88 - 3.95 (m, 3H). |
49% | With sodium methoxide; In N,N-dimethyl-formamide; at 0 - 20℃; for 12h; | To a stirred solution of 6-bromo-2-fluoropyridin-3-ol (4.67 g, 24.3 mmol) and sodium methoxide (1.38 g, 25.5 mmol) in N,N-dimethylformamide (50 mL) was added methyl iodide (1.59 mL, 25.5 mmol) at 0 C, and the mixture was stirred at room temperature for 12 hours. The mixture was treated with H20 and extracted with ethyl acetate. The combined organic layer was dried and evaporated. The residue was purified by chromatography on silica gel, eluting with ethyl acetate/ hexane (1: 5 v/v), to afford the titled compound as a yellow oil (2. 43 g, 49 %). 1H) NMR (270MHz, CDC13) 8 = 7.32-7. 26 (m, 1H), 7.22-7. 15 (m, 1H), 3.90 (s, 3H) ppm. MS (EI) ; M+=205, 207 |
With potassium carbonate; In acetone; at 60℃; for 14h;Inert atmosphere; | To a mixture of compound SI23-1 (2.00 g, 10.4 mmol, 1.00 eq) in acetone (30 mL) was added K2CO3 (2.88 g, 20.8 mmol, 2.00 eq) and CH3I (2.96 g, 20.8 mmol, 2.00 eq). The mixture was stirred at 60 C for 14 hrs. under N2 atmosphere. LC-MS (EC1719-5-P1A1) showed one peak (RT = 0.527 min) with desired MS = 205.8. The reaction mixture filtered and concentrated under reduced pressure to give a residue.Compound SI23-2 (2.10 g, crude) was obtained as a yellow solid.LCMS, EC1719-5-P1A1, RT = 0.527 min, M/Z (ESI): 205.8 (M+H)+. |
With potassium carbonate; In acetone; at 60℃; for 14h;Inert atmosphere; | To a mixture of compound SI23-1 (2.00 g, 10.4 mmol, 1.00 eq) in acetone (30 mL) was added K2CO3 (2.88 g, 20.8 mmol, 2.00 eq) and CH3I (2.96 g, 20.8 mmol, 2.00 eq). The mixture was stirred at 60 C for 14 hrs. under N2 atmosphere. LC-MS (EC1719-5-P1A1) showed one peak (RT = 0.527 min) with desired MS = 205.8. The reaction mixture filtered and concentrated under reduced pressure to give a residue.Compound SI23-2 (2.10 g, crude) was obtained as a yellow solid.LCMS, EC1719-5-P1A1, RT = 0.527 min, M/Z (ESI): 205.8 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
49% | In DMF (N,N-dimethyl-formamide); at 0 - 25℃; for 12h; | B. 6-bromo-2-fluoro-3-methoxypyridine; To a stirred solution of 6-bromo-2-fluoropyridin-3-ol (4.67 g, 24.3 mmol) and sodium methoxide (1.38 g, 25.5 mmol) in N, N dimethylformamide (50 mL) was added methyl iodide (1.59 mL, 25.5 mmol) at 0 C, and the mixture was stirred at room temperature for 12 hours. The mixture was treated with H20 and extracted with ethyl acetate. The combined organic layer was dried and evaporated. The residue was purified by chromatography on silica gel, eluting with ethyl acetate/hexane (1: 5 v/v), to afford the titled compound as a yellow oil (2.43 g, 49 %). 'H NMR (270MHz, CD13) 7.32-7. 26 (m, 1H), 7.22-7. 15 (m, 1H), 3.90 (s, 3H) ppm. MS (EI) ; M+=205, 207 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With 4-methyl-morpholine; In 1-methyl-pyrrolidin-2-one; at 120℃;Sealed tube; | A mixture of 6-bromo-2-fluoro-3-methoxy-pyridine (2.030 mmo 1; 418.1 mg), tert-butyl N-[(3S)-3-piperidyl]carbamate (3.044 mmol; 609.7 mg), and N-Methylmorpholine (6.089 mmol;622 mg; 0.676 mL) in 1-methyl-2-pyrrolidinone (5 mL) in a sealed pressure vial was heated at120 C overnight. The mixture was poured into water, and extracted with EtOAc. The organiclayer was concentrated. The residue was purified on silica eluted with 0 to 40% EtOAc in Heptane to afford tert-butyl N-[(3S)-1-(6-bromo-3-methoxy-2-pyridyl)-3-piperidyl]carbamate(743.5 mg, 95%). |
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