Crystals of phenylalanine derivatives and production methods thereof
The present invention provides crystals of phenylalanine derivatives of the formula (I): and particularly α-type, γ-type, ε-type, η-type, and θ-type crystals thereof. These crystals are excellent in preservation stability or moisture resistance. They can also be produced on an industrial scale.
1. A crystal of the compound of formula (I):
which is an α-type crystal which exhibits peaks at the diffraction angles (2θ) of at least 6.2°, 10.7°, and 14.0° in the powder X-ray diffraction pattern.
2. A crystal according to claim 1 , which exhibits peaks at the diffraction angles (2θ) of at least 6.2°, 10.7°, 10.8°, 14.0°, 16.2°, and 21.7° in the powder X-ray diffraction pattern.
3. A crystal according to claim 1 , which exhibits peaks at the diffraction angles (2θ) of at least 6.2°, 10.2°, 10.7°, 10.8°, 14.0°, 14.4°, 16.0°, 16.2°, and 21.7° in the powder X-ray diffraction pattern.
4. A method for producing an α-type crystal according to claim 1 , which comprises dissolving the compound of the formula (I) in a solvent which comprises at least one solvent selected from the group consisting of acetonitrile, dichloromethane, tetrahydrofuran, acetone, dimethylsulfoxide and chloroform, or in a mixed solvent of acetonitrile-water, or in a mixed solvent of acetonitrile dimethylformamide, to obtain a mixture; and cooling the mixture to 0 to 30° C. to obtain said crystal.
5. A method for producing an α-type crystal according to claim 1 , which comprises dissolving the compound of the formula (I) in a first solvent to obtain a mixture; and then adding a second solvent to said mixture to obtain said crystal, wherein the combination of said first solvent and said second solvent is selected from the group consisting of dimethylsulfoxide and toluene; dimethylformamide and diethylether; dimethylformamide and toluene; chloroform and ethanol; chloroform and toluene; chloroform and diethylether; dichloromethane and diethylether; tetrahydrofuran and water; tetrahydrofuran and cyclohexane; acetone and water; acetonitrile and water; and dimethylformamide and acetonitrile.
6. A method for producing an α-type crystal according to claim 1 , which comprises suspending the compound of formula (I) in acetonitrile, a mixed solvent of acetonitrile-water, or a mixed solvent of acetonitrile-dimethylformamide, to obtain a mixture; and stirring the mixture at 0 to 40° C. to obtain said crystal.
7. The method of claim 4 , wherein said mixture is cooled to 4 to 25° C. to obtain said crystal.
8. A method for producing an α-type crystal according to claim 2 , which comprises dissolving the compound of the formula (I) in a solvent which comprises at least one solvent selected from the group consisting of acetonitrile, dichloromethane, tetrahydrofuran, acetone, dimethylsulfoxide and chloroform, or in a mixed solvent of acetonitrile-water, or in a mixed solvent of acetonitrile-dimethylformamide, to obtain a mixture; and cooling the mixture to 0 to 30° C. to obtain said crystal.
9. The method of claim 8 , wherein said mixture is cooled to 4 to 25° C. to obtain said crystal.
10. A method for producing an α-type crystal according to claim 2 , which comprises dissolving the compound of the formula (I) in a first solvent to obtain a mixture; and then adding a second solvent to said mixture to obtain said crystal, wherein the combination of said first solvent and said second solvent is selected from the group consisting of dimethylsulfoxide and toluene; dimethylformamide and diethylether; dimethylformamide and toluene; chloroform and ethanol; chloroform and toluene; chloroform and diethylether; dichloromethane and diethylether; tetrahydrofuran and water; tetrahydrofuran and cyclohexane; acetone and water; acetonitrile and water; and dimethylformamide and acetonitrile.
11. A method for producing an α-type crystal according to claim 2 , which comprises suspending the compound of formula (I) in acetonitrile, a mixed solvent of acetonitrile-water, or a mixed solvent of acetonitrile-dimethylformamide, to obtain a mixture; and stirring the mixture at 0 to 40° C. to obtain said crystal.
12. A method for producing an α-type crystal according to claim 3 , which comprises dissolving the compound of the formula (I) in a solvent which comprises at least one solvent selected from the group consisting of acetonitrile, dichloromethane, tetrahydrofuran, acetone, dimethylsulfoxide and chloroform, or in a mixed solvent of acetonitrile-water, or in a mixed solvent of acetonitrile-dimethylformamide, to obtain a mixture; and cooling the mixture to 0 to 30° C. to obtain said crystal.
13. The method of claim 12 , wherein said mixture is cooled to 4 to 25° C. to obtain said crystal.
14. A method for producing an α-type crystal according to claim 3 , which comprises dissolving the compound of the formula (I) in a first solvent to obtain a mixture; and then adding a second solvent to said mixture to obtain said crystal, wherein the combination of said first solvent and said second solvent is selected from the group consisting of dimethylsulfoxide and toluene; dimethylformamide and diethylether; dimethylformamide and toluene; chloroform and ethanol; chloroform and toluene; chloroform and diethylether; dichloromethane and diethylether; tetrahydrofuran and water; tetrahydrofuran and cyclohexane; acetone and water; acetonitrile and water; and dimethylformamide and acetonitrile.
15. A method for producing an α-type crystal according to claim 3 , which comprises suspending the compound of formula (I) in acetonitrile, a mixed solvent of acetonitrile-water, or a mixed solvent of acetonitrile-dimethylformamide, to obtain a mixture; and stirring the mixture at 0 to 40° C. to obtain said crystal.