Process for producing crystal
View Patent ↗The present invention relates to a production method of a crystal of (R)-2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methyl]sulfinyl]benzimidazole·n′H 2 O (wherein n′ is about 0 to about 0.1) or a salt thereof, which characteristically includes crystallization from an organic solvent solution or suspension in which (R)-2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methyl]sulfinyl]-benzimidazole·nH 2 O (wherein n is about 0.1 to about 1.0) or a salt thereof has been dissolved or suspended, and the like, and provides a convenient method for efficiently producing an optically active sulfoxide derivative having an extremely high enantiomer excess in high yield at an industrial large scale.
1. A production method for a crystal of (R)-2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methyl]sulfinyl]benzimidazole·n′H 2 O (wherein n′ is about 0 to about 0.1) or a salt thereof, which comprises obtaining the crystal by crystallization from an organic solvent solution or suspension in which (R)-2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methyl]sulfinyl]benzimidazole·nH 2 O (wherein n is about 0.1 to about 1.0) or a salt thereof has been dissolved or suspended;
wherein the crystal of (R)-2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methyl]sulfinyl]benzimidazole·n′H 2 O (wherein n′ is about 0 to about 0.1) shows characteristic peaks at interplanar spacings(d) of 11.68, 6.77, 5.84, 5.73, 4.43, 4.09, 3.94, 3.89, 3.69, 3.41 and 3.11 Angstroms in powder X-ray diffraction.
2. A production method for a crystal of (S)-2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methyl]sulfinyl]benzimidazole·m′H 2 O (wherein m′ is about 0 to about 0.1) or a salt thereof, which comprises obtaining the objective crystal by crystallization from an organic solvent solution or suspension in which (S)-2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methyl]sulfinyl]benzimidazole·mH 2 O (wherein m is about 0.1 to about 1.0) or a salt thereof has been dissolved or suspended;
wherein the crystal of (S)-2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methyl]sulfinyl]benzimidazole·m′H 2 O (wherein m′ is about 0 to about 0.1) shows characteristic peaks at interplanar spacings(d) of 11.68, 6.77, 5.84, 5.73, 4.43, 4.09, 3.94, 3.89, 3.69, 3.41 and 3.11 Angstroms in powder X-ray diffraction.
3. A production method for a crystal of(R)-2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methyl]sulfinyl]benzimidazole·n′H 2 O (wherein n′ is about 0 to about 0.1) or a salt thereof, which is substantially free of (S)-2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methyl]sulfinyl]benzimidazole or a salt thereof, which method comprises obtaining a crystal of (R)-2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methyl]sulfinyl]benzimidazole·nH 2 O (wherein n is about 0.1 to about 1·0) or a salt thereof by way of a selective crystallization from a solution or suspension comprising (R)-2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methyl]sulfinyl]benzimidazole or a salt thereof in a greater amount than (S)-2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methyl]sulfinyl]benzimidazole or a salt thereof, followed by crystallization for the objective crystal from an organic solvent solution or suspension in which the said obtained crystal has been dissolved or suspended;
wherein the crystal obtained by the selective crystallization is
(1) a crystal showing characteristic peaks at interplanar spacings(d) of 5.88, 4.70, 4.35, 3.66 and 3.48 Angstroms in powder X-ray diffraction;
(2) a crystal showing characteristic peaks at interplanar spacings(d) of 8.33, 6.63, 5.86 and 4.82 Angstroms in powder X-ray diffraction; or
(3) a mixture of the crystals of the above (1) and (2).
4. A production method for a crystal of (R)-2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methyl]sulfinyl]benzimidazole·n′H 2 O (wherein n′ is about 0 to about 0.1) or a salt thereof, which is substantially free of(S)-2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methyl]sulfinyl]benzimidazole or a salt thereof, which method comprises obtaining a crystal of (R)-2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methyl]sulfinyl]benzimidazole·nH 2 O (wherein n is about 0.1 to about 1.0) or a salt thereof by way of a selective crystallization from a solution or suspension comprising (R)-2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methyl]sulfinyl]benzimidazole or a salt thereof in a greater amount than (S)-2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methyl]sulfinyl]benzimidazole or a salt thereof, followed by crystallization for the objective crystal from an organic solvent solution or suspension in which the said obtained crystal has been dissolved or suspended;
wherein the crystal of (R)-2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methyl]sulfinyl]benzimidazole·n′H 2 O (wherein n′ is about 0 to about 0.1) shows characteristic peaks at interplanar spacings(d) of 11.68, 6.77, 5.84, 5.73, 4.43, 4.09, 3.94, 3.89, 3.69, 3.41 and 3.11 Angstroms in powder X-ray diffraction.
5. A production method for a crystal of(S)-2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methyl]sulfinyl]benzimidazole·m′H 2 O (wherein m′ is about 0 to about 0.1) or a salt thereof, which is substantially free of (R)-2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methyl]sulfinyl]benzimidazole or a salt thereof, which method comprises obtaining a crystal of (S)-2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methyl]sulfinyl]benzimidazole·mH 2 O (wherein m is about 0.1 to about 1.0) or a salt thereof by a selective crystallization from a solution or suspension comprising (S)-2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methyl]sulfinyl]benzimidazole or a salt thereof in a greater amount than (R)-2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methyl]sulfinyl]benzimidazole or a salt thereof, followed by crystallization for the objective crystal from an organic solvent solution or suspension in which the obtained crystal has been dissolved or suspended;
wherein the crystal of (S)-2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methyl]sulfinyl]benzimidazole·m′H 2 O (wherein m′ is about 0 to about 0.1) shows characteristic peaks at interplanar spacings(d) of 11.68, 6.77, 5.84, 5.73, 4.43, 4.09, 3.94, 3.89, 3.69, 3.41 and 3.11 Angstroms in powder X-ray diffraction.
6. A production method for a crystal of(R)-2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methyl]sulfinyl]benzimidazole or a salt thereof, which is substantially free of (S)-2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methyl]sulfinyl]benzimidazole or a salt thereof, which method comprises obtaining a crystal of (R)-2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methyl]sulfinyl]benzimidazole or a salt thereof by a selective crystallization from a solution comprising (R)-2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methyl]sulfinyl]benzimidazole or a salt thereof in a greater amount than (S)-2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methyl]sulfinyl]benzimidazole or a salt thereof and subjecting the obtained crystal to a dehydration step, followed by crystallization for the objective crystal;
wherein the crystal obtained by the selective crystallization is
(1) a crystal showing characteristic peaks at interplanar spacings(d) of 5.88, 4.70, 4.35, 3.66 and 3.48 Angstroms in powder X-ray diffraction;
(2) a crystal showing characteristic peaks at interplanar spacings(d) of 8.33, 6.63, 5.86 and 4.82 Angstroms in powder X-ray diffraction; or
(3) a mixture of the crystals of the above (1) and (2).
7. A production method for a crystal of (S)-2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methyl]sulfinyl]benzimidazole·m′H 2 O (wherein m′ is about 0 to about 0.1) or a salt thereof, which is substantially free of(R)-2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methyl]sulfinyl]benzimidazole or a salt thereof, which method comprises obtaining a crystal of (S)-2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methyl]sulfinyl]benzimidazole·mH 2 O (wherein m is about 0.1 to about 1.0) or a salt thereof by a selective crystallization from a solution or suspension comprising (S)-2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methyl]sulfinyl]benzimidazole or a salt thereof in a greater amount than (R)-2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methyl]sulfinyl]benzimidazole or a salt thereof, followed by crystallization for the objective crystal from an organic solvent solution or suspension in which the obtained crystal has been dissolved or suspended;
wherein the crystal obtained by the selective crystallization is
(1) a crystal showing characteristic peaks at interplanar spacings(d) of 5.88, 4.70, 4.35, 3.66 and 3.48 Angstroms in powder X-ray diffraction;
(2) a crystal showing characteristic peaks at interplanar spacings(d) of 8.33, 6.63, 5.86 and 4.82 Angstroms in powder X-ray diffraction; or
(3) a mixture of the crystals of the above (1) and (2).
8. A production method for a crystal of (S)-2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methyl]sulfinyl]benzimidazole or a salt thereof, which is substantially free of (R)-2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methyl]sulfinyl]benzimidazole or a salt thereof which method comprises obtaining a crystal of (S)-2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methyl]sulfinyl]benzimidazole or a salt thereof by a selective crystallization from a solution comprising (S)-2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methyl]sulfinyl]benzimidazole or a salt thereof in a greater amount than (R)-2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methyl]sulfinyl]benzimidazole or a salt thereof, and subjecting the obtained crystal to a dehydration step, followed by crystallization for the objective crystal;
wherein the crystal obtained by the selective crystallization is
(1) a crystal showing characteristic peaks at interplanar spacings(d) of 5.88, 4.70, 4.35, 3.66 and 3.48 Angstroms in powder X-ray diffraction;
(2) a crystal showing characteristic peaks at interplanar spacings(d) of 8.33, 6.63, 5.86 and 4.82 Angstroms in powder X-ray diffraction; or
(3) a mixture of the crystals of the above (1) and (2).