JPS6034941B2 - Production method of fluoromalonate ester - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing a fluoromalonate ester, and more particularly to a novel method for producing a dialkyl 2-fluoromalonate using hexafluoroproben as a raw material.

The above dialkyl 2-fluoromalonate has the formula: [In the formula, R and R' each represent a lower alkyl group.

] The compound is useful as an intermediate for the synthesis of fluorine-containing organic compounds as physiologically active substances.

For example, fluorobarbic acids useful as hypnotic agents can be produced by subjecting this to chemical conversion as shown in the following formula: [In the formula, R'' is a hydrocarbon group having 1 to 10 carbon atoms, and X is Represents a halogen atom.

R and R' are the same as above. Conventionally, the above-mentioned dialkyl 2-fluoromalonate has been prepared by 1) condensing ethyl fluoroacetate and ethyl chloroformate in the presence of a base, and 2) heating diethyl fluorooxalate derived from ethyl fluoroacetate and diethyl oxalate. 3. A method of halogen exchange of diethyl chloromalonate with potassium fluoride or its hydrogen fluoride adduct at high temperature; 4. A method of fluorinating diethylmalonate with perchloryl fluoride (CI03F); 5
It is produced by adding methoxide ion to trifluoroacrylic acid.

However, the raw materials for these production methods are expensive, toxic, require long reaction steps, and cannot be said to be desirable because the desired product cannot be obtained in good yield. In the course of a series of studies, the present inventors discovered a new method for producing dialkyl 2-fluoromalonate in good yield using hexafluoroproben as a raw material, and completed the present invention.

That is, the gist of the present invention is {a} expression: CF2=CFCF3 Hexafluoroprobene shown as Formula: , ROM [In the formula, M represents an alkali metal.

R is the same as above. ] and the alkoxide represented by the formula: ROH [In the formula, R is the same as above.

] to react in the presence of an alcohol represented by the formula: R
HiF2C Town CF3 [In the formula, R is the same as above.

1,1,2,3,3,3-hexafluoropropyl alkyl ether represented by
, 1,2,3,3,3-hexafluor.

Propyl alkyl ether is hydrolyzed in the presence of an acid or treated with an acid in the presence of silicon dioxide to form the formula:
In the formula, R is the same as above.

] was obtained, and {c) the 2,3,3 obtained in {b} above was obtained.
, 3-tetrafluoropropionate with the formula: R'OM' [wherein M' represents an alkali metal.

R' is the same as above. ] is reacted with an alkoxide represented by the formula: ROH in the presence of an alcohol represented by ROH [wherein R is the same as above], and then hydrolyzed in the presence of the formula: Same as.

] The present invention relates to a method for producing a fluoromalonate ester, which is characterized by obtaining a dialkyl 2-fluoromalonate represented by the following.

According to the method of the present invention, the target substance can be produced by a simple process as shown in the following formula using hexafluoroprobene, which is easily available and has low toxicity, as a starting material.
The total yield is also good (50-55%).

In step 'a, R in ROM represents a lower alkyl group having 1 to 4 carbon atoms, preferably methyl or ethyl.

Further, M is an alkali metal, preferably sodium. Alcohols are used as the solvent, preferably lower alcohols (eg, methanol, ethanol, prop/ol, etc.). The reaction temperature is not particularly limited, but it is usually 20 OO or less, preferably 1 OO or less and above the freezing point of the solvent. In step [b}', the reaction is usually carried out in the presence of an acid by adding a stoichiometric amount of water.

As the acid, ordinary hydrogen acid is used, but organic acids such as concentrated sulfuric acid, fuming sulfuric acid, fluorosulfuric acid, and trifluoromethanesulfonic acid are preferably used. Moreover, these acids may be allowed to act in the presence of an oxide such as silicon dioxide instead of the water described above. The reaction temperature is not particularly limited, but is usually 8000 or less, preferably 3000 to 1000. In step (c,
The reaction is usually carried out in the presence of the same range of alkoxides as used in step a, using alcohol as the reaction solvent.

The reaction temperature is generally 20° C. or lower, above the freezing point of the solvent, preferably 0° C. or below. The treatment under acidic conditions is carried out at around room temperature in the presence of a common key acid such as hydrochloric acid by adding a stoichiometric amount of water, and the desired product can be easily obtained.

Note that separation and purification of the target product from the reaction mixture may be carried out according to conventional methods.

The present invention will be specifically described below with reference to Examples.

Example 1 90% of sodium methoxide (1.74 mol) was dissolved in 500% of methanol, and 255% of hexafluoroprobene was dissolved.
g (1.70 mol) is absorbed over a period of 3 hours at a temperature above 1000 °C.

After reacting for several more minutes at room temperature, the reaction mixture was poured into ice water and the oil layer was separated to give 400% of the crude product of 1,1,2,3,3,3-hexafluoropropyl ether. I got it. Place this in a PoIJ ethylene container and heat under 400 liters of concentrated sulfuric acid. After completion, the reaction mixture is allowed to float for an additional hour at room temperature and poured into ice water. The oil layer is separated, washed with an aqueous sodium bicarbonate solution, washed with water, and dried over magnesium sulfate. Distillation yields 203 g of methyl 2,3,3,3-tetrafluoropropionate. Boiling point 94-96
00. Yield 74%. This was added dropwise to a solution of 205 g (3.8 mol) of sodium methoxide in 800 methanol kept at 0° C., and reacted at room temperature for 30 minutes. The reaction mixture is acidified with concentrated hydrochloric acid, the distilled methanol is removed and the residue is extracted with ether. The extracts are washed successively with aqueous sodium bicarbonate solution and water and dried over magnesium sulfate. Distillation under reduced pressure was performed to obtain 107 g of dimethyl 2-fluoromalonate. Boiling point 111-11 on 0/45 side Hg. Yield 71%. Example 2 2,3,3,3-tetrafluoropropionic acid was produced in a yield of 82% by the same procedure as in Example 1 except that sodium methoxide was replaced with sodium ethoxide and methanol was replaced with ethanol. Ethyl (boiling point 108-109
2-fluoromalonate diethyl (110-11100/20 Hg) was obtained with a yield of 63%.

Claims (1)

[Claims] 1 (a) Hexafluoropropene represented by the formula: CF_2=CFCF_3 is represented by the formula: ROM [wherein, R represents a lower alkyl group and M represents an alkali metal]. ] and the alkoxide represented by the formula: ROH [wherein R is the same as above. ] to react in the presence of an alcohol represented by the formula: R
OCF_2CHFCF_3 [wherein R is the same as above. ] to obtain 1,1,2,3,3,3-hexafluoropropylalkyl ether, (b) 1,1,2,3,3,3-hexafluoropropylalkyl obtained in (a) above. By hydrolyzing ether in the presence of an acid or acting with an acid in the presence of silicon dioxide, ▲There are mathematical formulas, chemical formulas, tables, etc.▼ [In the formula, R is the same as above. ] to obtain the alkyl 2,3,3,3-tetrafluoropropionate represented by (c) the 2,3,3 obtained in (b) above.
, 3-tetrafluoropropionate is represented by the formula: R'OM' [wherein, R' represents a lower alkyl group and M' represents an alkali metal. ] and the alkoxide represented by the formula: R'OH [wherein R' is the same as above. ] followed by hydrolysis in the presence of an acid to form the formula: ▲Mathematical formulas, chemical formulas, tables, etc.▼ [In the formula, R and R' are the same as above. ] A method for producing a fluoromalonate ester, characterized by obtaining a dialkyl 2-fluoromalonate represented by the following.