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Chemical Structure| 635708-74-6 Chemical Structure| 635708-74-6

Structure of 635708-74-6

Chemical Structure| 635708-74-6

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Product Details of [ 635708-74-6 ]

CAS No. :635708-74-6
Formula : C9H13Cl
M.W : 156.65
SMILES Code : CC(C)(C)C#C/C=C\CCl
MDL No. :MFCD08460526

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Application In Synthesis of [ 635708-74-6 ]

* 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.

  • Downstream synthetic route of [ 635708-74-6 ]

[ 635708-74-6 ] Synthesis Path-Downstream   1~1

  • 1
  • [ 65473-13-4 ]
  • [ 635708-74-6 ]
  • [ 287471-30-1 ]
  • [ 78628-80-5 ]
  • N-(6,6-dimethyl-2-hepten-4-ynyl)-N-methyl-1-naphthylmethyl amine hydrochloride [ No CAS ]
YieldReaction ConditionsOperation in experiment
124.8 grams (0.601 mole) N-methyl-1-naphthylmethyl amine (III) HCl followed by 120 grams (1.1 mole) sodium carbonate were added to 720 ml tap water in a three-necked reactor with stirring at 300-350 rpm. The reaction mixture was heated to 77-83 C. 93.6 grams (0.598 mole) 1-chloro-6,6-dimethyl-2-heptene-4-yne (IVb), obtained as described above were added over a four-hour period. After 4 additional hours at 80 C., stirring was ceased, leading to an immediate appearance of two phases. The lower aqueous phase was removed from the reactor and washed with toluene (2×100 ml). The two toluene washes and an additional 720 ml toluene were added to the reactor. The toluene solution was allowed to cool to room temperature. 66 ml of a 32% aqueous HCl solution were added to the toluene solution so as to acidify the solution to a pH of about 0.5-1.5 as measured using a Gel Pressure Electrode, produced by Mettler-Toledo International. After 20 minutes, 200 ml water were added, and the resulting suspension was stirred at 20-30 C. for 15 minutes and then filtered using Whatman No. 1 filter paper. The cake was washed with toluene (3×120 ml) and with water (1×150 ml). The damp cake was dried at 50 C. for 5 hours, to give 174 gram of a mixture containing the hydrochloride salts of Terbinafine (I) and the Terbinafine cis isomer (II) (0.555 mole, 93.8% yield relative to IVb).; 124.8 grams (0.601 mole) N-methyl-1-naphthylmethyl amine (III) HCl followed by 120 grams (1.1 mole) sodium carbonate were added to 720 ml tap water in a three-necked reactor with stirring at 300-350 rpm. The reaction mixture was heated to 77-83 C. 93.6 grams (0.598 mole) 1-chloro-6,6-dimethyl-2-heptene-4-yne (IVb) (3.5:1 trans/cis ratio) were added over a four-hour period. After 4 additional hours at 80 C., stirring was ceased, leading to an immediate appearance of two phases. The lower aqueous phase was removed from the reactor and washed with toluene (2×100 ml). The two toluene washes and an additional 720 ml toluene were added to the reactor. The toluene solution was allowed to cool to room temperature. Gaseous HCl was bubbled through the solution over a period of 20 minutes until the pH reached 1.5 as measured using a Gel Pressure Electrode, produced by Mettler-Toledo International. The reaction was exothermic, the temperature of the solution rising from 30 C. to 50 C. in 30 minutes. The reaction was allowed to cool to room temperature. After 20 minutes, 200 ml water were added, and the resulting suspension was stirred at 20-30 C. for 15 minutes and then filtered using Whatman No. 1 filter paper. The cake was washed with toluene (3×120 ml) and water (1×150 ml). The damp cake was dried at 50 C. for 5 hours, to give 182 grams of a mixture containing the hydrochloride salts of Terbinafine (I) and the Terbinafine cis isomer (II) (0.580 mole, 97.1% yield relative to IVb).; Example 5 Large-Scale Preparation of Terbinafine HCl 100 kilograms (482 mole) N-methyl-1-naphthylmethyl amine (III) HCl followed by 95 kilograms (800 mole) sodium carbonate were added to 550 liter tap water in a 1000 liter reactor with stirring. The reaction mixture was heated to 77-83 C. 75 kilogram (479 mole) 1-chloro-6,6-dimethyl-2-heptene-4-yne (IVb) (4:1 trans/cis ratio) were added over a four hour period. After 2 additional hours at 77-83 C., stirring was ceased, leading to the appearance of two phases. The lower aqueous phase was removed, 570 liters toluene were added to the reactor, mixed for 15 minutes, and removed. The aqueous phase was returned to the reactor and mixed with 80 liters toluene for 15 minutes. After an additional 15 minutes, the aqueous phase was removed and the previously removed product-containing toluene solution returned to the reactor. The toluene solution was allowed to cool to 20 C.-25 C. 60 liters of a 32% aqueous HCl solution were added to the toluene solution, so as to acidify the solution over a period of two hours while the temperature was maintained at 20 C.-25 C. Once the addition of HCl was completed, it was confirmed that the pH of the solution was less than 1.5, and mixing continued for an additional 15 minutes. The suspension was then filtered (using a filter pressure). The cake was washed with 100 liters toluene, then with 200 liters water and then with another 100 liters toluene. The damp cake was dried at 50 C. for 12 hours under a nitrogen stream to obtain 140 kilogram of a mixture containing the hydrochloride salts of Terbinafine (I) and the Terbinafine cis isomer (II) (446 mole, 93.1% yield relative to IVb).
 

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