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CAS No. : | 110860-92-9 | MDL No. : | MFCD09835219 |
Formula : | C5H3Cl2NO | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | GMHPKIGFTDRQBP-UHFFFAOYSA-N |
M.W : | 163.99 | Pubchem ID : | 14391672 |
Synonyms : |
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Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H302-H315-H319-H335 | Packing Group: | N/A |
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 nitrite; In sulfuric acid; water; toluene; | EXAMPLE 11 5,6-dichloro-3-pyridinol Process (a) 8.15 g (50 mmol) of <strong>[98121-41-6]3-amino-5,6-dichloropyridine</strong> were dissolved in 100 ml of 8N H2 SO4 and diazotized at 0 C. using 3.55 g (53 mmol) of sodium nitrite in 9 ml of water. The cold diazonium salt solution was added dropwise to 100 C. warm 60% strength sulfuric acid. After completion of the nitrogen elimination, the mixture was neutralized and extractively distilled using toluene. The dried toluene phase was concentrated by evaporation and the residue was recrystallized repeatedly from toluene. Melting point 184-185 C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
39% | With triphenylphosphine; diethylazodicarboxylate; | 109b. 5,6-Dichloro-3-(1-t-butyloxycarbonyl-2-(S)-azetidinylmethoxy)pyridine N-Boc-2-(S)-azetidinol from Example 7b (1.55 g, 8.28 mmol), triphenylphosphine (2.6 g, 9.94 mmol), DEAD (1.6 mL, 9.94 mmol), and 5,6-dichloro-3-hydroxypyridine (1.5 g, 9.10 mmol) were allowed to react as in Example 9. The crude product was chromatographed eluding with EtOAc:hexane (1:5) to give 1.08 g of a waxy solid, 39% yield. MS (CI) m/e 333 (M+H)+. 1 H NMR (CDCl3, 300 MHz) d 7.97 (d, J=2.8 Hz, 1H), 7.41 (d, J=2.8 Hz, 1H), 4.56-4.48 (m, 1H), 4.40-4.30 (m, 1H), 4.12 (dd, J=10.1, 2.7 Hz, 1H-), 3.95-3.82 (m, 2H), 2.42-2.22 (m, 2H), 1.42 (s, 9H). |
39% | With triphenylphosphine; diethylazodicarboxylate; | 109b. 5,6-Dichloro-3-(1-t-butyloxycarbonyl-2-(S)-azetidinylmethoxy)pyridine N-Boc-2-(S)-azetidinol from Example 7b (1.55 g, 8.28 mmol), triphenylphosphine (2.6 g, 9.94 mmol), DEAD (1.6 mL, 9.94 mmol), and 5,6-dichloro-3-hydroxypyridine (1.5 g, 9.10 mmol) were allowed to react as in Example 9. The crude product was chromatographed eluding with EtOAc:hexane (1:5) to give 1.08 g of a waxy solid, 39% yield. MS (CI) m/e 333 (M+H)+. 1 H NMR (CDCl3, 300 MHz) δ: 7.97 (d, J=2.8 Hz, 1H), 7.41 (d, J=2.8 Hz, 1H), 4.56-4.48 (m, 1H), 4.40-4.30 (m, 1H), 4.12 (dd, J=10.1, 2.7 Hz, 1H), 3.95-3.82 (m, 2H), 2.42-2.2 (m, 2H), 1.42 (s, 9H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
7% | With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 6h; | A mixture of 5,6-dichloropyridin-3-ol (PREPARATION 15, 3.28 g, 20.0 mmol), <strong>[1354961-13-9]tert-butyl 5-chloro-2,4-difluorobenzoate</strong> (PREPARATION WO 2012007883, 4.96 g, 20.0 mmol) and potassium carbonate (4.15 g, 30.0 mmol) in anhydrous N,N-dimethylformamide (30 mL) was stirred at ambient temperature for 6 h followed by filtration. The residue was washed with ethyl acetate (100 mL). The filtrate was washed with saturated solution of ammonium chloride (3 x 20 mL), brine (3 x 20 mL), dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated in vacuo and the residue was purified via silica gel column chromatography eluting with ethyl acetate in hexanes using 10-30% gradient to afford the title compound (0.51 g, 7% yield) as a colourless solid: NMR (300 MHz, CDC13) δ 8.09 (d, J= 2.7 Hz, 1H), 8.00 (d, J= 7.3 Hz, 1H), 7.41 (d, J= 2.7 Hz, 1H), 6.74 (d, J= 10.4 Hz, 1H), 1.58 (s, 9H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triphenylphosphine; In tetrahydrofuran; dichloromethane; | 15a. 5-((2S)-azetidinylmethoxy)-2,3-dichloropyridine hydrochloride A solution of triphenylphosphine (2.6 g, 9.94 mmol) and diethyl azodicarboxylate (1.6 mL, 9.94 mmol) in THF (16 mL) was stirred at 0 C. for 15 minutes. 1-t-Butyloxycarbonyl-2-(S)-azetidinemethanol (1.55 g, 8.28 mmol, from step 7c above) and 5,6-dichloro-3-pyridinol (1.5 g, 9.1 mmol) were then added. The reaction mixture was allowed to warm slowly to room temperature and stir overnight. The solvent was removed, and the residue was redissolved in methylene chloride. The solution was washed with saturated aqueous K2 CO3 and brine, dried over MgSO4 and concentrated. The residue was chromatographed (silica gel; ethyl acetate:hexane, 1:5) to afford the 5,6-dichloro-3-(1-t-butyloxycarbonyl-2-(S)-azetidinylmethoxy)pyridine (1.08 g): MS (CI/NH3) m/z 333 (M+H)+; 1 H NMR (CDCl3, 300 MHz) δ 1.42 (s, 9H), 2.22-2.42 (m, 2H), 3.85-3.92 (m, 2H), 4.12 (dd, J=2.7, 10.1 Hz, 1 H), 4.30-4.40 (m, 1 H), 4.48-4.56 (m, 1 H), 7.41 (d, J=2.8 Hz, 1 H), 7.97 (d, J=2.8 Hz, 1 H). |
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