* 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.
With potassium hydroxide; In polyethylene glycol-400 (PEG-400); at 25 - 40℃; for 5h;
In a 3-necked round bottom flask, N-methyl-naphthylmethylamine hydrochloride (2 g) and PEG-400 (15 ml) were added at room temperature (about 25 C. to about 30 C.) and stirred for about 15 minutes. Trans-1-chloro-6,6-dimethyl-2-heptene-4-yne (2 g) was added to the round bottom flask. A first lot of potassium hydroxide powder (0.2 g) was added to the flask at room temperature and maintained for about 1 hour. A second lot of potassium hydroxide powder (0.4 g) was added to the flask and maintained for about 1 hour. A third lot of potassium hydroxide powder (0.4 g) was added to the flask and the contents of the flask were heated to a temperature ranging from about 35 C. to about 40 C. for about 3 hours. The completion of the reaction was monitored by TLC. After completion of the reaction as determined by TLC, water (150 ml) was added to the flask. The terbinafine was extracted from the flask with toluene (4 volumes). The toluene layer was washed with 2% tartaric acid solution. The toluene was distilled off under a vacuum and the contents were cooled to room temperature.
With sodium hydroxide; sodium borohydrid; In isopropyl alcohol; toluene;
EXAMPLE 16 0.5 g of 1-(2'-furyl)-2,2-dimethylpropan-1-one 4-methoxybenzenesulfonyl hydrazone (1.49 mmol) prepared in Example 3 and 0.06 g of sodium hydroxide (1.59 mmol) were added to 10 ml of toluene. The reaction mixture was stirred for two hours at 90 C., cooled to room temperature, and washed with 10 ml of distilled water and 10 ml of 2N-hydrochloride acid (twice). 0.23 g of <strong>[65473-13-4]N-methyl-1-naphthalenemethylamine hydrochloride</strong> (1.11 mmol) and 0.04 g of sodium borohydride (1.1 mmol) were added to the reaction mixture, which was then stirred for an hour at room temperature. 14 ml of isopropanol was added to the reaction mixture, which was then stirred for thirty-six hours at room temperature, washed with 35 ml of 2N-hydrochloric acid twice, and concentrated under a reduced pressure. The resulting mixture was purified with silica gel column chromatography (ethyl acetate/hexane=1/20) to give 0.03 g of terbinafine (yield: 9.3%).
With sodium carbonate; In water; at 10 - 75℃; for 6.75h;Product distribution / selectivity;
Example-6: Preparation of crystalline Form-I of Terbinafine compound of formula-3 Added 60 grams of sodium carbonate to a solution of 75 grams of N-methyl naphthylmethyl amine hydrochloride in 450 ml of water and at an ambient temperature. Stirred the reaction mixture for 45 minutes at an ambient temperature. Cooled the reaction mixture to 10-150C. Added 112.5 grams of 6,6-dimethyl-l-chlorohept-2-ene-4-yne to the above reaction mixture at 10-15C. Heated the reaction mixture to 70-750C. Stirred the reaction mixture for 6 hours at 70-750C. Cooled the reaction mixture to 25-35C. Quenched the reaction mixture with water. Extracted the reaction mixture thrice with methylene chloride. Combined all the organic phases and washed thrice with water. Separated the organic phase. Distilled the organic phase completely under reduced pressure at below 500C. Added 50 ml of isopropyl alcohol to the above reaction mixture. Distilled the solvent completely under reduced pressure at below 500C. Cooled the reaction mixture to 25-350C. Added 180 ml of isopropyl alcohol to the above reaction mixture and heated to reflux. Stirred the reaction mixture at reflux for 20 minutes. Cooled the reaction mixture to 0-50C. Stirred the reaction mixture for 60 minutes at 0-50C. Filtered the <n="24"/>precipitated solid and washed with chilled isopropyl alcohol. Dried the material to get the crystalline Form-I of Terbinafme. Yield: 74 grams
With sodium carbonate; In water; N,N-dimethyl-formamide; at 10 - 75℃; for 6.75h;Product distribution / selectivity;
Example-7: Preparation of crystalline Form-I of Terbinafine compound of formula-3Added 60 grams of sodium carbonate to a solution of 75 grams of N-methyl naphthylmethyl amine hydrochloride in 450 ml of water and of dimethylformamide at an ambient temperature. Stirred the reaction mixture for 45 minutes at an ambient temperature. Cooled the reaction mixture to 10-15C. Added 112.5 grams of 6,6-dimethyl- l-chlorohept-2-ene-4-yne to the above reaction mixture at 10-15C. Heated the reaction mixture to 70-75C. Stirred the reaction mixture for 6 hours at 70-75C. Cooled the reaction mixture to 25-35C. Quenched the reaction mixture with water. Extracted the reaction mixture thrice with methylene chloride. Combined all the organic phases and washed thrice with water. Separated the organic phase. Distilled the organic phase completely under reduced pressure at below 5O0C. Added 50 ml of ethyl acetate to the above reaction mixture. Distilled the solvent completely under reduced pressure at below 60C. Cooled the reaction mixture to 25-35C. Added 180 ml of ethyl acetate to the above reaction mixture and heated to reflux. Stirred the reaction mixture at reflux for 20 minutes. Cooled the reaction mixture to 0-5C. Stirred the reaction mixture for 60 minutes at 0-5C. Filtered the precipitated solid and washed with chilled ethyl acetate. Dried the material to get the crystalline Form-I of Terbinafine. Yield: 72 gramsExampIe-8: Preparation of crystalline Form-I of Terbinafine compound of formula-3 Added 60 grams of sodium carbonate to a solution of 75 grams of N-methyl naphthylmethyl amine hydrochloride in 450 ml of water and 100 ml of dimethyl formamide at an ambient temperature. Stirred the reaction mixture for 45 minutes at an ambient temperature. Cooled the reaction mixture to 10-150C. Added 112.5 grams of 6,6-dimethyl-l-chlorohept-2-ene-4-yne to the above reaction mixture at 10-150C. Heated the reaction mixture to 70-75C. Stirred the reaction mixture for 6 hours at 70-750C. Cooled the reaction mixture to 25-350C. Quenched the reaction mixture with water. <n="25"/>Extracted the reaction mixture thrice with methylene chloride. Combined all the organic phases and washed thrice with water. Separated the organic phase. Distilled the organic phase completely under reduced pressure at below 50C. Added 50 ml of acetone to the above reaction mixture. Distilled the solvent completely under reduced pressure at below 60C. Cooled the reaction mixture to 25-35C. Added 180 ml of acetone to the above reaction mixture and heated to reflux. Stirred the reaction mixture at reflux for 20 minutes. Cooled the reaction mixture to 0-5C. Stirred the reaction mixture for 60 minutes at 0-5C. Filtered the precipitated solid and washed with chilled acetone. Dried the material to get the crystalline Form-I of Terbinafme. Yield: 73 grams
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