WO2008015714A2 - Process for the preparation of 1,1-dichloro-2-alkylethylene - Google Patents

Process for the preparation of 1,1-dichloro-2-alkylethylene Download PDF

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WO2008015714A2
WO2008015714A2 PCT/IT2007/000529 IT2007000529W WO2008015714A2 WO 2008015714 A2 WO2008015714 A2 WO 2008015714A2 IT 2007000529 W IT2007000529 W IT 2007000529W WO 2008015714 A2 WO2008015714 A2 WO 2008015714A2
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dichloro
process according
butyl
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PCT/IT2007/000529
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WO2008015714A3 (en
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Marco Fachini
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F.I.S. Fabbrica Italiana Sintetici S.P.A.
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C17/00—Preparation of halogenated hydrocarbons
    • C07C17/26—Preparation of halogenated hydrocarbons by reactions involving an increase in the number of carbon atoms in the skeleton
    • C07C17/263—Preparation of halogenated hydrocarbons by reactions involving an increase in the number of carbon atoms in the skeleton by condensation reactions
    • C07C17/269—Preparation of halogenated hydrocarbons by reactions involving an increase in the number of carbon atoms in the skeleton by condensation reactions of only halogenated hydrocarbons
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C209/00—Preparation of compounds containing amino groups bound to a carbon skeleton
    • C07C209/68—Preparation of compounds containing amino groups bound to a carbon skeleton from amines, by reactions not involving amino groups, e.g. reduction of unsaturated amines, aromatisation, or substitution of the carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C211/00—Compounds containing amino groups bound to a carbon skeleton
    • C07C211/01—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms
    • C07C211/26—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing at least one six-membered aromatic ring
    • C07C211/30—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing at least one six-membered aromatic ring the six-membered aromatic ring being part of a condensed ring system formed by two rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
    • C07C51/16—Preparation of carboxylic acids or their salts, halides or anhydrides by oxidation
    • C07C51/29—Preparation of carboxylic acids or their salts, halides or anhydrides by oxidation with halogen-containing compounds which may be formed in situ

Definitions

  • reaction between isopropyl chloride and vinylidene chloride in the presence of aluminium trichloride produces 1, l-dichloro-3-methyl-1-butene with a yield of 30%.
  • 1, 1-dichloro- 2-cyclohexylethylene is obtained starting from cyclohexyl chloride with an yield of 30-50%.
  • Both 1,1- dichloro-3, 3-dimethyl-1-butene and 1, 1, l-trichloro-3 , 3- dimethylbutane produce t-butylacetic acid through hydrolysis .
  • One of the key synthons used in this process is the t- butylacetylene lithium salt, in turn prepared by treatment of 1, l-dichloro-3, 3-dimethylbutene with a base such as butyllithium:
  • 1, l-dichloro-3, 3-dimethylbutene is prepared via reaction of t-butyl chloride and vinylidene chloride in the presence of iron trichloride with a yield close to that similar processes known in the literature, that is between 41 and 58%. Even the GC purities indicated are also quite poor and variable between 93% and 95%. After further studies it was found that one of the main impurities of 1, l-dichloro-3,3-dimethylbutene, thus prepared, was its higher homologous, 1, l-dichloro-3, 3- dimethylpentene, found approximately at 1%.
  • the object of the present invention is to provide 1,1- dichloro-3,3-dimethylbutene and its analogues at high yields, with high purity and substantially free of 1,1- dichloro-3,3-dimethylpentene analogues thereof.
  • Another object of the present invention is to provide Terbinafin, prepared according to the teachings of WO
  • R represents a group such as secondary or tertiary C 3 -C 5 alkyl , C 3 -C 5 alkenyl or a secondary or tertiary C 3 -C 6 cycloalkyl , C 3 -C 6 cycloalkenyl , comprising reacting 1 , 1-dichloroethylene with an alkylating agent selected from the group consisting of R-X alkyl halide , wherein X represents chlorine , bromine or iodine and wherein R bears the meaning indicated above; an R-OH alcohol wherein R bears the meaning indicated above; an R' COOR ester wherein R' represents a C 1 -C 4 alkyl group and wherein R bears the meaning indicated above; an ROR or R'OR ether wherein R and R' bear the meaning indicated above; an olefin with 3 to 5 carbon atoms capable of producing an R + carbocation, wherein R bears the meaning described above; a cycloole
  • a process for the preparation of 1, l-dichloro-3, 3-dimethylbutene comprising reacting 1, 1-dichloroethylene with t-butyl chloride in the presence of a Lewis acid metal halide characterised in that the amount of 1, 1-dichloroethylene used is greater than 1.5 times that of said alkylating agent .
  • R is selected from a group consisting of isopropyl, t-butyl, 2-butyl, 2-methyl-2-butyl, 2-pentyl, 3-pentyl, cyclopropyl, cyclopentyl, cyclohexyl, propenyl, 3-cyclohexenyle, 4-cyclohexenyle; more preferably R is t-butyl .
  • the alkylating agent is an R-X alkyl halide, wherein R and X bear the meaning described above.
  • the alkylating agent is preferably selected from the group consisting of t-butyl chloride, t- butanol, t-butyl acetate, t-butyl methyl ether and isobutene .
  • the molar amount of 1, 1-dichloroethylene used is greater than 2 times that of said alkylating agent .
  • the metal halide is selected from the group consisting of iron trichloride, aluminium trichloride, iron tribromide, aluminium tribromide, zinc dichloride, tin tetrachloride, titanium tetrachloride, bismuth trichloride; more preferably, the metal halide is selected between iron trichloride and aluminium trichloride; most preferably the metal is iron trichloride.
  • the molar ratio of metal halide used is between 0.05 and 0.20 with respect to the alkylating agent mentioned above.
  • the reaction is preferably carried out in a solvent selected from the group consisting of methylene chloride, trichlorobenzene and nitrobenzene.
  • a solvent selected from the group consisting of methylene chloride, trichlorobenzene and nitrobenzene.
  • Technical effect results from the use of excess 1,1- dichloroethylene which acts as a hydrochloric acid scavenger, thus producing 1, 1, 1-trichloroethane.
  • This is a common chlorinated solvent easily removable by- distillation.
  • 1,1- dichlorpethylene solves the problem of secondary reactions leading to the production of 1, l-dichloro-3 , 3- dimethylpentene and other impurities .
  • Prior art documents use approximately stoichiometric amounts of vinylidene chloride and alkylating agent. However, these documents do not state that poor yields and purities can be enhanced considerably by using excess vinylidene chloride .
  • Such product quality is used in the Terbinafin synthesis described in WO 2005/121155, by reacting (E) -N- (3-haloallyl) -N- trimethylsilylmethanamine, preferably (E) -N- (3- chloroallyl) -N- trimethylsilylmethanamine, with t- butylacetylene lithium salt, thus obtaining a product with a homo-terbinafina impurity content of 0.03%, hence lower than 0.10%.
  • t-butylacetylene lithium salt is the result of the reaction between 1, l-dichloro-3, 3- dimethylbutene and butyllithium.
  • the impurity content of 1, l-dichloro-3, 3-dimethylpentene is not substantially reduced through distillation of 1, l-dichloro-3, 3- dimethylbutene on columns with a low number of theoretical stages. For this reason, obtaining a crude product substantially free of said impurity beforehand is of paramount importance.
  • the present invention provides a simple method for preparing 1, l-dichloro-3, 3-dimethylbutene and its analogues having the following advantages: a) A 30 percentage points higher yield than that of the preparative methods known in the literature; b) A greater than 99% purity of the product thus obtained, compared to 93-95% of the known methods; c) An impurity content of 1, l-dichloro-3 , 3- dimethylpentene or its analogues below or equivalent to
  • 1, l-dichloro-3, 3-dimethylbutene and 1, l-dicloro-2- alchyl-1-ethylenes thus prepared are useful intermediates in the synthesis of t-butylacetylene and 2-alkylacetylenes or salts thereof respectively, or else, for fc-butylacetic acid and 2-alkylacetic acids or salts thereof.
  • Example 1 1, l-dichloro-3, 3-dimethylbutene 20 g of anhydrous iron trichloride are suspended into 100 ml of methylene chloride, in an inert nitrogen environment. A mixture consisting of t-butyl chloride

Abstract

The object of the present invention is a process for the preparation of 1,1-dichloro-2-alkyl-1-ethylene and in particular, 1, 1-dichloro-3,3-dimethyl-1-butene. These compounds are useful intermediates for the preparation of the corresponding 2-alkylacetylenes and salts thereof alongside the corresponding 2-alkylacetic acids.

Description

DESCRIPTION "Process for the preparation of l,l-dichloro-2- alkylethylene" Technical field of the invention This invention concerns a process for the preparation of 1, l-dichloro-2-alkyl-l-ethylene and in particular, 1,1- dichloro-3, 3 -dimethyl-1-butene. These compounds are useful intermediates for the preparation of the equivalent 2-alkylacetylenes and the respective salts alongside the corresponding 2-alkylacetic acids.
Background art
Condensation of alkyl chlorides with 1, 1-dichloroethylene (vinylidene chloride) in the presence of Lewis acids acting as catalysts is an ideal method for preparing 1,1- dichloro-2-alkyl-l-ethylene. Thus, for instance, reaction between t-butyl chloride and vinylidene chloride catalysed by iron trichloride leads to 1, l-dichloro-3, 3- dimethyl-1-butene, as stated by Schmerling in J. Am. Chem. Soc. 71, 701 (1949) and in US 2481159. However, the article mentioned beforehand shows how the synthesis produces a mixture of the same product with 1,1,1- trichloro-3,3-dimethylbutane. The reaction temperature is indicated as the decisive factor. However, under the best reaction conditions, the yield in 1, l-dichloro-3 , 3- dimethyl-1-butene is only 60%.
Likewise, reaction between isopropyl chloride and vinylidene chloride in the presence of aluminium trichloride produces 1, l-dichloro-3-methyl-1-butene with a yield of 30%. Under similar conditions, 1, 1-dichloro- 2-cyclohexylethylene is obtained starting from cyclohexyl chloride with an yield of 30-50%. Both 1,1- dichloro-3, 3-dimethyl-1-butene and 1, 1, l-trichloro-3 , 3- dimethylbutane produce t-butylacetic acid through hydrolysis .
Figure imgf000003_0001
In Chem. Ber. 103, 1216-1224 (1970) Viehe and Delavarenne prepare 1, l-dichloro-3, 3-dimethyl-1-butene starting from t-butyl chloride e vinylidene chloride using aluminium trichloride as a catalyst. Even in this case the yield is quite poor (55%) .
In Tetrahedron Lett. 41, 4007 - 4009 (2000), Wang et al . use l,l-dichloro-2-alkyl-i-ethylenes as useful intermediates for the synthesis in the corresponding alkylacetylenes . For instance, 1, l-dichloro-2 cyclopropylethylene is reacted with methyllithium to give cyclopropylacethylene in a 95% yield based on raw material and 89% after distillation. Cyclopropylacethylene is one of the main raw materials used for the synthesis of Efavirenz (Sustiva) , an anti- HIV active ingredient.
In WO 2005/121155 F. I. S. claims a process for the preparation of Terbinafin, chemically known as (E) -N- (6, 6-dimethyl-2-hepten-4-ynyl) -N-methyl-1- naphthalenemethanamine, an antimycotic drug for topical and oral use with the following chemical structure:
Figure imgf000004_0001
One of the key synthons used in this process is the t- butylacetylene lithium salt, in turn prepared by treatment of 1, l-dichloro-3, 3-dimethylbutene with a base such as butyllithium:
Figure imgf000004_0002
1, l-dichloro-3, 3-dimethylbutene is prepared via reaction of t-butyl chloride and vinylidene chloride in the presence of iron trichloride with a yield close to that similar processes known in the literature, that is between 41 and 58%. Even the GC purities indicated are also quite poor and variable between 93% and 95%. After further studies it was found that one of the main impurities of 1, l-dichloro-3,3-dimethylbutene, thus prepared, was its higher homologous, 1, l-dichloro-3, 3- dimethylpentene, found approximately at 1%.
Figure imgf000005_0001
This impurity gives 3 , 3-dimethyl-1-pentyne lithium salt, through treatment with butyllithium, leading to the presence in the final product of the impurity we termed "homo-terbinafina" , that is (E) -N- (6, 6-dimethyl-2-octen- 4-ynyl) -N-methyl-1-naphthalenemethanamine :
Figure imgf000005_0002
Due to its structural similarity with Terbinafin, this impurity cannot be efficiently purified through crystallisation from Terbinafin. The object of the present invention is to provide 1,1- dichloro-3,3-dimethylbutene and its analogues at high yields, with high purity and substantially free of 1,1- dichloro-3,3-dimethylpentene analogues thereof.
Another object of the present invention is to provide Terbinafin, prepared according to the teachings of WO
2005/121155, with a homo-terbinafina residual content lower or equivalent to 0.10%.
Short description of the invention
An improved process for the preparation of 1, 1-dichloro- 2-alkyl-1-ethylene and in particular, 1, l-dichloro-3 , 3- dimethyl-1-butene starting from 1, 1-dichloroethylene was surprisingly found which comprises the use of an excess of 1 , 1-dichloroethylene .
Detailed description of the invention A process is provided for the preparation of 1,1- dichloro-2-alkyl-l-ethylene of formula 1
R Cl
Cl 1 wherein R represents a group such as secondary or tertiary C3-C5 alkyl , C3-C5 alkenyl or a secondary or tertiary C3-C6 cycloalkyl , C3-C6 cycloalkenyl , comprising reacting 1 , 1-dichloroethylene with an alkylating agent selected from the group consisting of R-X alkyl halide , wherein X represents chlorine , bromine or iodine and wherein R bears the meaning indicated above; an R-OH alcohol wherein R bears the meaning indicated above; an R' COOR ester wherein R' represents a C1-C4 alkyl group and wherein R bears the meaning indicated above; an ROR or R'OR ether wherein R and R' bear the meaning indicated above; an olefin with 3 to 5 carbon atoms capable of producing an R+ carbocation, wherein R bears the meaning described above; a cycloolefin with 3 to 6 carbon atoms capable of producing an R+ carbocation, wherein R bears the meaning described above; in the presence of a Lewis acid metal halide, characterised in that the molar amount of 1,1- dichloroethylene used is greater than 1.5 times that of said alkylating agent .
In particular, a process is provided for the preparation of 1, l-dichloro-3, 3-dimethylbutene comprising reacting 1, 1-dichloroethylene with t-butyl chloride in the presence of a Lewis acid metal halide characterised in that the amount of 1, 1-dichloroethylene used is greater than 1.5 times that of said alkylating agent . Preferably, R is selected from a group consisting of isopropyl, t-butyl, 2-butyl, 2-methyl-2-butyl, 2-pentyl, 3-pentyl, cyclopropyl, cyclopentyl, cyclohexyl, propenyl, 3-cyclohexenyle, 4-cyclohexenyle; more preferably R is t-butyl .
Preferably, the alkylating agent is an R-X alkyl halide, wherein R and X bear the meaning described above. Otherwise, the alkylating agent is preferably selected from the group consisting of t-butyl chloride, t- butanol, t-butyl acetate, t-butyl methyl ether and isobutene .
Preferably, the molar amount of 1, 1-dichloroethylene used is greater than 2 times that of said alkylating agent .
Preferably, the metal halide is selected from the group consisting of iron trichloride, aluminium trichloride, iron tribromide, aluminium tribromide, zinc dichloride, tin tetrachloride, titanium tetrachloride, bismuth trichloride; more preferably, the metal halide is selected between iron trichloride and aluminium trichloride; most preferably the metal is iron trichloride. Preferably, the molar ratio of metal halide used is between 0.05 and 0.20 with respect to the alkylating agent mentioned above.
The reaction is preferably carried out in a solvent selected from the group consisting of methylene chloride, trichlorobenzene and nitrobenzene. Technical effect results from the use of excess 1,1- dichloroethylene which acts as a hydrochloric acid scavenger, thus producing 1, 1, 1-trichloroethane. This is a common chlorinated solvent easily removable by- distillation. By scavenging hydrochloric acid, 1,1- dichlorpethylene solves the problem of secondary reactions leading to the production of 1, l-dichloro-3 , 3- dimethylpentene and other impurities . Prior art documents use approximately stoichiometric amounts of vinylidene chloride and alkylating agent. However, these documents do not state that poor yields and purities can be enhanced considerably by using excess vinylidene chloride .
After a simple work-up, following this invention it is possible to obtain crude 1, l-dichloro-3 , 3-dimethylbutene in quantitative yield and low 1, l-dichloro-3, 3- dimethylpentene impurity contents, below or equivalent to 0.1%. Crude 1, l-dichloro-3, 3-dimethylbutene is appropriately purified through distillation, at atmospheric pressure or under vacuum, obtaining a 89% yield of distillate, purity above 99% (GC) and a 1,1- dichloro-3, 3 -dimethylpentene impurity content lower or equivalent to 0.1%. Such product quality is used in the Terbinafin synthesis described in WO 2005/121155, by reacting (E) -N- (3-haloallyl) -N- trimethylsilylmethanamine, preferably (E) -N- (3- chloroallyl) -N- trimethylsilylmethanamine, with t- butylacetylene lithium salt, thus obtaining a product with a homo-terbinafina impurity content of 0.03%, hence lower than 0.10%. t-butylacetylene lithium salt is the result of the reaction between 1, l-dichloro-3, 3- dimethylbutene and butyllithium. The impurity content of 1, l-dichloro-3, 3-dimethylpentene is not substantially reduced through distillation of 1, l-dichloro-3, 3- dimethylbutene on columns with a low number of theoretical stages. For this reason, obtaining a crude product substantially free of said impurity beforehand is of paramount importance.
In conclusion, the present invention provides a simple method for preparing 1, l-dichloro-3, 3-dimethylbutene and its analogues having the following advantages: a) A 30 percentage points higher yield than that of the preparative methods known in the literature; b) A greater than 99% purity of the product thus obtained, compared to 93-95% of the known methods; c) An impurity content of 1, l-dichloro-3 , 3- dimethylpentene or its analogues below or equivalent to
0.1%.
1, l-dichloro-3, 3-dimethylbutene and 1, l-dicloro-2- alchyl-1-ethylenes thus prepared are useful intermediates in the synthesis of t-butylacetylene and 2-alkylacetylenes or salts thereof respectively, or else, for fc-butylacetic acid and 2-alkylacetic acids or salts thereof.
Other characteristics and advantages of the process of the invention will appear from the description of preferred preparation examples given as illustrative but not limiting examples. Examples
Example 1: 1, l-dichloro-3, 3-dimethylbutene 20 g of anhydrous iron trichloride are suspended into 100 ml of methylene chloride, in an inert nitrogen environment. A mixture consisting of t-butyl chloride
(2.16 mol) and 500 g of vinylidene chloride (5.16 mol,
2.4 eq.) is added drop-wise at 250C, under reasonable stirring. Halfway through the addition, 8 g of iron trichloride are added and at the end thereof another 2 g are added. After one hour, the reaction mass is transferred into a flask containing 200 ml of water and the phases are separated. The organic phase is washed with water and then with a 5% sodium bicarbonate solution. Next, the resulting mixture is distilled, at atmospheric pressure, on a Vigreux column until the trichloroethane content is substantially reduced, then a moderate vacuum is applied and distillation of the product is continued. 295 g (1.93 mmol , 89%) of 1, l-dichloro-3 , 3- dimethylbutene are obtained as a clear colourless liquid with 99.33% GC purity, 0.05% of 1, l-dichloro-3 , 3- dimethylpentene content, 0.57% of 1, 1, 1-trichloroethane content . Example 2 : 1 , l-dichloro-3 , 3 -dimethylbutene .
The process outlined in example 1 is repeated using 600 g (6.19 mol, 2.9 eq.) of vinylidene chloride instead of 500 g. 250 g (1.64 mol, 76%) of 1, l-dichloro-3 , 3- dimethylbutene are obtained with 99.92 % GC purity and 0.03% of 1, l-dicloro-3,3-dimethylpentene content. Compared to the previous example, the lower yield observed is due to the non-ideal distillation conditions .

Claims

1. Process for the preparation of 1, l-dichloro-2- alkyl-1-ethylene of formula 1
R Cl
Cl
1 wherein R represents a group such as secondary or tertiary C3-C5 alkyl, C3-C5 alkenyl o secondary or tertiary C3-C6 cycloalkyl, or C3-C6 cycloalkenyl comprising reacting 1, 1-dichloroethylene with an alkylating agent selected from the group consisting of R-X alkyl halide, wherein X represents chlorine, bromine or iodine and wherein R bears the meaning indicated above; an R-OH alcohol wherein R bears the meaning indicated above; an R' COOR ester wherein R' represents a C1-C4 alkyl group and wherein R bears the meaning indicated above; an ROR or R'OR ether wherein R and R' bear the meaning indicated above; an olefin with 3 to 5 carbon atoms capable of producing an R+ carbocation, wherein R bears the meaning described above; a cycloolefin with 3 to 6 carbon atoms capable of producing an R+ carbocation, wherein R bears the meaning described above; in the presence of a Lewis acid metal halide, characterised in that the amount of 1,1-dichloroethylene used is greater than 1.5 times that of said alkylating agent .
2. Process according to claim 1 wherein R is selected from the group consisting of isopropyl, t-butyl, 2- butyl, 2-methyl-2-butyl, 2-pentyl, 3-pentyl, cyclopropyl, cyclopentyl, cyclohexyl, propenyl, 3- cyc1ohexeny1 , 4-eye1ohexenyl .
3. Process according to anyone of the previous claims wherein R is t-butyl.
4. Process according to anyone of the previous claims wherein the alkylating agent is an R-X alkyl halide.
5. Process according to claims 1-3 wherein the alkylating agent is selected from the group consisting of t-butyl chloride, t-butanol, t-butyl acetate, t-butyl methyl ether and isobutene.
6. Process according to anyone of the previous claims wherein the molar amount of I71-dichloroethylene used is greater than 2 times that of said alkylating agent.
7. Process according to anyone of the previous claims wherein the metal halide is selected from the group consisting of iron trichloride, aluminium trichloride, iron tribromide, aluminium tribromide, zinc dichloride, tin tetrachloride, titanium tetrachloride, bismuth trichloride .
8. Process according to anyone of the previous claims wherein the metal halide is iron trichloride.
9. Process according to anyone of the previous claims wherein metal halide is used in a molar ration between 0.05 and 0.20 with respect to the alkylating agent.
10. Process according to anyone of the previous claims wherein the reaction is carried out in a solvent selected from a group including methylene chloride, trichlorobenzene and nitrobenzene.
11. Process according to anyone of the previous claims also comprising the preparation step of 2- alkylacethylene or salts thereof starting from 1,1- dichloro-2-alkyl-l-ethylene 1.
12. Process according to claims 1-10 also comprising the preparation step of 2-alkylacetic acid or salts thereof starting from 1, l-dichloro-2-alkyl-l-ethylene 1.
13. Process for the preparation of 1, l-dichloro-3, 3- dimethylbutene comprising reacting 1, 1-dichloroethylene with t-butyl chloride in the presence of a Lewis acid metal halide characterised in that molar amount of 1,1- dichloroethylene used is greater than 1.5 times that of said alkylating agent.
14. Process according to claim 13 also comprising the preparation step of t-butylacetylene o salts thereof starting from 1, l-dichloro-3, 3-dimethylbutene.
15. Process according to claim 13 also comprising the preparation step of t-butylacetic acid or salts thereof starting from 1, l-dichloro-3,3-dimethγlbutene.
16. Terbinafin synthesis process also comprising the step of reacting (E) -N- (3-haloallyl) -N- trimethylsilylmethanamine with t-butylacetylene lithium salt wherein the t-butylacetylene lithium salt is obtained from the reaction between 1, l-dichloro-3 , 3- dimethylbutene and butyllithium, characterised in that said 1, l-dichloro-3, 3-dimethylbutene is obtained through the process according to claims 13-15.
PCT/IT2007/000529 2006-08-04 2007-07-26 Process for the preparation of 1,1-dichloro-2-alkylethylene WO2008015714A2 (en)

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112661586A (en) * 2020-12-29 2021-04-16 山东铂源药业有限公司 Preparation method of 3,3-dimethyl-1-butyne
CN114195631A (en) * 2021-12-20 2022-03-18 大连奇凯医药科技有限公司 Preparation process of 3, 3-dimethylbutyric acid

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US4492795A (en) * 1981-11-19 1985-01-08 Bayer Aktiengesellschaft Alkylcycloalkyl imidazolylmethyl ketones as fungicide intermediates
US4878939A (en) * 1985-11-15 1989-11-07 Bayer Aktiengesellschaft Fungicidal and plant-growth regulating azolyl ether ketones and alcohols
WO2005121155A1 (en) * 2004-06-09 2005-12-22 F.I.S. Fabbrica Italiana Sintetici S.P.A. A process for the synthesis of terbinafine and derivatives thereof

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4492795A (en) * 1981-11-19 1985-01-08 Bayer Aktiengesellschaft Alkylcycloalkyl imidazolylmethyl ketones as fungicide intermediates
US4878939A (en) * 1985-11-15 1989-11-07 Bayer Aktiengesellschaft Fungicidal and plant-growth regulating azolyl ether ketones and alcohols
WO2005121155A1 (en) * 2004-06-09 2005-12-22 F.I.S. Fabbrica Italiana Sintetici S.P.A. A process for the synthesis of terbinafine and derivatives thereof

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112661586A (en) * 2020-12-29 2021-04-16 山东铂源药业有限公司 Preparation method of 3,3-dimethyl-1-butyne
CN112661586B (en) * 2020-12-29 2022-06-21 山东铂源药业股份有限公司 Preparation method of 3,3-dimethyl-1-butyne
CN114195631A (en) * 2021-12-20 2022-03-18 大连奇凯医药科技有限公司 Preparation process of 3, 3-dimethylbutyric acid
CN114195631B (en) * 2021-12-20 2024-03-29 大连奇凯医药科技有限公司 Preparation process of 3, 3-dimethylbutyric acid

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