JPS5811867B2 - Method for producing 5,5-dimethyl-4-phenyloxazolidin-2-one derivative - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention is based on the general formula (where R is a hydrogen atom or a phenyl group, and R' and R'' are the same or different and are a hydrogen atom or a methyl group).

n represents an integer from 0 to 3, respectively.

) The present invention relates to a method for producing N-substituted-5,5-dimethyl-4-hydroxy-4-phenyloxazolidin-2-one represented by the following formula.

The present invention further relates to the general formula (wherein R, R', R'' and n have the same meanings as above).

) The present invention relates to a method for producing N-substituted-5,5-dimethyl-4-phenyloxazolidin-2-one represented by

According to the method of the present invention, 1-lower alkoxy-1,2-epoxy-2-methyl-
For 1 mole of 1-phenylpropane, the general formula (where R is a hydrogen atom or a phenyl group, R' and R'' are the same or different, and n is a hydrogen atom or a methyl group is 0 to 0)
Each represents an integer of 3.

) Add 2 to 3 moles of the amine shown below to saturate with carbon dioxide.

By gently heating at 60 to 80°C for 4 to 6 hours, the target compound [■] can be obtained.Also, the compound [
(2)] is dissolved in a lower alkyl alcohol, a small amount of concentrated hydrochloric acid is added, and catalytic reduction is carried out in a conventional manner to obtain the other target compound (11) of the present invention.

In the above reaction, methanol, ethanol, propatool, butanol, etc. are used as the lower alkyl alcohol solvent.

Carbon dioxide gas or dry ice can be used as carbon dioxide.

When ammonia or aniline is used as the amine, it is preferable to carry out the reaction in a sealed tube.

The above raw material compound CIII) is, for example, published in The Journal
on the American Chemical Society, 72,
It can be produced according to the method described on page 4758 (1950).

Compounds [■] and (II) obtained according to the present invention are important as medicines, particularly as psychotropic drugs.

Example 1 7.4 g of isopropylamine was dissolved in 20 ml of methanol, and this solution was saturated with carbon dioxide gas.

Process 8.9 g of 1,2-epoxy-2-methyl-1-methoxy-1-phenylpropane into a saturated solution.

The reaction was carried out by heating at 70°C for 4 hours.

After the reaction was completed, methanol was distilled off, the residue was washed with petroleum ether, and then recrystallized from a benzene-acetone mixed solution.

10.2 g of purified crystals of N-isopropyl-5,5-dimethyl-4-hydroxy-4-phenyloxasolidin-2-one were obtained.

Yield 81.9%. Melting point 180°C Calculated value (%) as elemental analysis value C14H1903N C, 67,47H, 7,630,19,2
8N, 5.62 Measured value (%) C, 67, 15H, 7, 6
00,19,47N, 5.78 Example 2 Add 8.9 g of ammonia water to 20 ml of methanol and dissolve 8.9 g of 1° 2-epoxy-2-methyl-1-methoxy-1-phenylpropane, This solution was saturated with carbon dioxide gas and placed in a sealed tube.

The reaction was carried out by heating at 60° C. for 4 hours.

The solvent was distilled off from the reaction-completed solution, and the residue was washed with petroleum ether.

Recrystallized from a benzene-acetone mixed solution to give 5°5-
8.2 g of purified crystals of dimethyl-4-hydroxy-4-phenyloxazolidin-2-one were obtained.

Yield 79.2%, melting point 173°C Elemental analysis values C1, H1
Calculated value (%) as 303N C, 63,77H, 6,280,23,1
9N, 6.76 Measured value (%) C, 63,84H, 6,3
10,23,07N, 6.78 Example 3 10.8 g of benzylamine was dissolved in 20 ml of methanol, and 1,2-epoxy-2-methyl-1-methoxy-1-phenylpropane 8. '1 was added, and a small piece of dry ice was added to saturate the mixture.

This was subjected to a gentle heating reaction at 60° C. for 3 hours.

Methanol was distilled off from the reaction completed solution, the residue was washed with petroleum ether, and then recrystallized from a benzene-acetone mixed solution to obtain N-benzyl-5,5-dimethyl-4-hydroxy-4-phenyloxazolidine- 12.4 g of purified crystals of 2-one were obtained.

Yield 82.9%, melting point 168°C Elemental analysis value Calculated value (%) as Cl8H1,03N C,72,73H,6,400,16,1
6N, 4.71 Actual value (%) C, 72,59H, 6,4
40,16,24N, 4.83 Example 4 3.0 g of N-isopropyl-5゜5-dimethyl-4-hydroxy-4-phenyloxazolidin-2-one was dissolved in 100 ml of methanol, and then 100 mg of palladium on carbon was dissolved. After the addition, hydrogen was introduced and the solution was reacted with stirring.

The catalyst was removed from the reaction completed solution, methanol was distilled off from the filtrate, and the residue was recrystallized from a benzene-petroleum ether mixed solution to obtain N-isopropyl-5,5-dimethyl-4-phenyloxabridine- 2.6 g of purified crystals of 2-one were obtained.

Yield 92.2%, melting point 54°C Elemental analysis value Calculated value (%) as C14H1902N C,72,10H,8,150,13,7
3N, 6.00 Measured value (%) C, 71,97H, 8,2
10,13,68N, 6.14 Example 5 N-benzyl-5,5-dimethyl-4-hydroxy-4-phenyloxazolidine- in 10 M methanol
Dissolve 3.0g of 2-one and then add 10g of palladium on carbon.
After adding 0 mg, hydrogen was introduced.

The solution was allowed to react while stirring.

The catalyst was removed from the reaction solution, methanol was distilled off, and the residue was recrystallized from benzene to obtain N-benzyl-5,5-
2.7 g of purified crystals of dimethyl-4-phenyloxazolidin-2-one were obtained.

Yield 95.0%, melting point 103°C Elemental analysis value Cl8H Calculated value (%) as 790°N C, 76,87H, 6,760, 11,3
9N, 4.98 measured value (%) C, 77, 40H, 6,7
00, 11, 14N, 5.12 Example 6 The following compound was produced in the same manner as in Example 1, 2 or 3.

N-Methyl-5,5-dimethyl-4-noAhydroxy-4-phenyloxazolidin-2-one.

Melting point 188°C N-ethyl-5,5-dimethyl-4-hydroxy-
4-phenyloxazolidin-2-one.

Melting point 143°C N-phenyl-5,5-dimethyl-4-hydroxy-4-phenyloxazolidin-2-one, melting point 215
°C N-cyclohexyl-5,5-dimethyl-4-hydroxy-4-phenyloxazolidin-2-one, melting point 245 °C Example 7 The following compound was produced in the same manner as in Example 4. .

N-methyl-5,5-dimethyl-4-phenyloxazolidin-2-one, melting point 88°C

Claims (1)

[Claims] 1 General formula (wherein R is a hydrogen atom, a cyclohexyl group, or a phenyl group, R' and R'' are the same or different and are a hydrogen atom or a methyl group, and n is an integer of 0 to 3) ) and carbon dioxide, and 1-lower alkoxy-1,2-epoxy- represented by the general formula (in the formula, R'' represents a lower alkyl group).
It is characterized by reacting with 2-methyl-1-phenylpropane. A method for producing N-substituted-5,5-dimethyl-4-hydroxy-4-phenyloxazolidin-2-one represented by the general formula (wherein R2R' and R" have the same meanings as above). 2 General formula (In the formula, R is a hydrogen atom or a phenyl group, R' and R'' are the same or different and represent a hydrogen atom or a methyl group, and n represents an integer from 0 to 3, respectively.) An amine, carbon dioxide, and 1-4, alkoxy 1,2-epoxy-2-methyl-1-phenylpropane represented by the general formula (in the formula, R'' represents a lower alkyl group) is reacted with the resulting general formula (formula R, R' and R'' have the same meanings as above. do. A method for producing N-substituted-5,5-dimethyl-4-phenyloxazolidin-2-one represented by the general formula (wherein R, R' and R'' have the same meanings as above).