Claims
- 1. A process for crystallizing N.sup.2 ((S)-1-ethoxycarbonyl-3-phenylpropyl)-N.sup.6 -trifluoroacetyl-L-lysyl-L-proline which comprises first crystallizing said N.sup.2 -((S)-1-ethoxycarbonyl-3-phenylpropyl)-N.sup.6 -trifluoroacetyl-L-lysyl-L-proline from a solution of said N.sup.2 -((S)-1-ethoxycarbonyl-3-phenylpropyl)-N.sup.6 -trifluoroacetyl-L-lysyl-L-proline where a sufficient amount of at least one compound is used as a solvent, and then completing crystallization by successively adding a sufficient amount of auxiliary solvent for controlling crystallizing conditions, said compound having a property that said N.sup.2 -((S)-1-ethoxycarbonyl-3-phenylpropyl)-N.sup.6 -trifluoroacetyl-L-lysyl-L-proline can be crystallized from said solution therewith and having the general formula:
- CR.sup.1 R.sup.2 R.sup.3 R.sup.4
- wherein R.sup.1 is chlorine atom, bromine atom, methoxy group, acetyl group, acetoxy group, chloromethyl group or phenyl group; R.sup.2 is hydrogen atom, chlorine atom, bromine atom, methyl group, ethyl group or methoxy group; R.sup.3 is chlorine atom, bromine atom, methyl group or methoxy group; R.sup.4 is chlorine atom, bromine atom, methyl group or methoxy group; provided that the combination, and wherein R.sup.1 is methoxy group and R.sup.3 and R.sup.4 are methyl group is excluded.
- 2. The process for crystallizing as set forth in claim 1, wherein said compound is selected from the group consisting of methyl tert-butyl ketone, tert-butylbenzene, phenyltrichloromethane, carbon tetrabromide, isopropyl acetate, tert-butyl acetate, 2,2-dimethoxypropane, trimethyl orthoacetate, tetramethyl orthocarbonate, isobutyl chloride, tert-butyl chloride, 2,2-dichloropropane, 1,1,1-trichloroethane, carbon tetrachloride, 1,1,2-trichloroethane, neopentyl chloride, 2,2-dichlorobutane and bromotrichloromethane.
- 3. The process for crystallizing as set forth in claim 1, wherein said auxiliary solvent is selected from the group consisting of n-hexane, cyclohexane and methylcyclohexane.
- 4. The process for crystallizing as set forth in claim 2, wherein said auxiliary solvent is selected from the group consisting of n-hexane, cyclohexane and methylcyclohexane.
- 5. The process for crystallizing as set forth in claim 1, wherein said solvent consists of methyl tert-butyl ether and at least one of said compound.
- 6. The process for crystallizing of claim 2, wherein said solvent consists of methyl tert-butyl ether and at least one of said compound.
- 7. The process for crystallizing as set forth in claim 3, wherein said solvent consists of methyl tert-butyl ether and at least one of said compound.
- 8. A process for crystallizing N.sup.2 (S)-1-ethoxycarbonyl-3-phenylpropyl)-N.sup.6 -trifluoroacetyl-L-lysyl-L-proline, which comprises providing said N.sup.2 -((S)-1-ethoxycarbonyl-3-phenylpropyl)-N.sup.6 -trifluoroacetyl-L-lysyl-L-proline in a solution with a first solvent, replacing at least a portion of said first solvent with a compound and crystallizing N.sup.2 -((S)-1-ethoxycarbonyl-3-phenylpropyl)-N.sup.6 -trifluoroacetyl-L-lysyl-L-proline from the resultant replaced solution of N.sup.2 -((S)-1-ethoxycarbonyl-3-phenylpropyl)-N.sup.6 -trifluoroacetyl-L-lysyl-L-proline, said compound being different than said first solvent and having a property that said N.sup.2 -((S)-1-ethoxycarbonyl-3-phenylpropyl)-N.sup.6 -trifluoroacetyl-L-lysyl-L-proline can be crystallized from said solution therewith and having the general formula:
- CR.sup.1 R.sup.2 R.sup.3 R.sup.4
- wherein R.sup.1 is chlorine atom, bromine atom, methoxy group, acetyl group, acetoxy group, chloromethyl group or phenyl group; R.sup.2 is hydrogen atom, chlorine atom, bromine atom, methyl group, ethyl group or methoxy group; R.sup.3 is chlorine atom, bromine atom, methyl group or methoxy group; R.sup.4 is chlorine atom, bromine atom, methyl group or methoxy group; provided that the combination, and wherein R.sup.1 is methoxy group and R.sup.3 and R.sup.4 are methyl group is excluded.
- 9. The process for crystallizing as set forth in claim 8, wherein said compound is selected from the group consisting of methyl tert-butyl ketone, tert-butylbenzene, phenyltrichloromethane, carbon tetrabromide, isopropyl acetate, tert-butyl acetate, 2,2-dimethoxypropane, trimethyl orthoacetate, tetramethyl orthocarbonate, isobutyl chloride, tert-butyl chloride, 2,2-dichloropropane, 1,1,1-trichloroethane, carbon tetrachloride, 1,1,2-trichloroethane, neopentyl chloride, 2,2-dichlorobutane and bromotrichloromethane.
- 10. The process for crystallizing as set forth in claim 8, wherein said first solvent is replaced with a mixed solvent of said compound and auxiliary solvent for controlling crystallizing conditions.
- 11. The process of crystallizing as set forth in claim 8, wherein said crystallizing is first crystallization and thereafter crystallization is completed by successively adding a sufficient amount of methylcyclohexane.
- 12. The process for crystallizing as set forth in claim 9, wherein said first solvent is replaced with a mixed solvent of said compound and auxiliary solvent for controlling crystallizing conditions.
- 13. The process for crystallizing as set forth in claim 10, wherein said auxiliary solvent is selected from the group consisting of n-hexane, cyclohexane and methylcyclohexane.
- 14. The process for crystallizing as set forth in claim 12, wherein said auxiliary solvent is selected from the group consisting of n-hexane, cyclohexane and methylcyclohexane.
- 15. A process for crystallizing N.sup.2 -((S)-1-ethoxycarbonyl-3-phenylpropyl)-N.sup.6 -trifluoroacetyl-L-lysyl-L-proline, which comprises first crystallizing N.sup.2 -((S)-1-ethoxycarbonyl-3-phenylpropyl)-N.sup.6 -trifluoroacetyl-L-lysyl-L-proline wherein a sufficient amount of methyl tert-butyl ether is used as a solvent and then completing crystallization by successively adding a sufficient amount of methylcyclohexane.
- 16. A process for crystallizing N.sup.2 -((S)-1-ethoxycarbonyl-3-phenylpropyl)-N.sup.6 -trifluoroacetyl-L-lysyl-L-proline, which comprises providing a solution of said N.sup.2 -((S)-1-ethoxycarbonyl-3-phenylpropyl)-N.sup.6 -trifluoroacetyl-L-lysyl-L-proline in a solution with a first solvent other than methyl tert-butyl ether, replacing at least a portion of said first solvent with said methyl tert-butyl ether, first crystallizing said N.sup.2 -((S)-1-ethoxycarbonyl-3-phenylpropyl)-N.sup.6 -trifluoroacetyl-L-lysyl-L-proline from the resultant replaced solution of N.sup.2 -((S)-1-ethoxycarbonyl-3-phenylpropyl)-N.sup.6 -trifluoroacetyl-L-lysyl-L-proline, and completing crystallization by successively adding a sufficient amount of methylcyclohexane.
- 17. A process for crystallizing N.sup.2 -((S)-1-ethoxycarbonyl-3-phenylpropyl)-N.sup.6 -trifluoroacetyl-L-lysyl-L-proline, which comprises providing said N.sup.2 -((S)-1-ethoxycarbonyl-3-phenylpropyl)-N.sup.6 -trifluoroacetyl-L-lysyl-L-proline in a solution with a first solvent other than methyl tert-butyl ether and/or methylcyclohexane, replacing at least a portion of said first solvent with a mixed solvent of said methyl tert-butyl ether and said methylcyclohexane, and crystallizing N.sup.2 -((S)-1-ethoxycarbonyl-3-phenylpropyl)-N.sup.6 -trifluoroacetyl-L-lysyl-L-proline from the resultant replaced solution of N.sup.2 -((S)-1-ethoxycarbonyl-3-phenylpropyl)-N.sup.6 -trifluoroacetyl-L-lysyl-L-proline.
Priority Claims (1)
Number |
Date |
Country |
Kind |
2044/1993 |
Jan 1993 |
JPX |
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CROSS-REFERENCE TO RELATED APPLICATION
This application is a divisional application of U.S. Ser. No. 08/295,649, filed on Aug. 26, 1994, now U.S. Pat. No. 5,519,146.
US Referenced Citations (6)
Foreign Referenced Citations (6)
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Date |
Country |
0215335 |
Mar 1987 |
EPX |
61-36297 |
Feb 1986 |
JPX |
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Jun 1987 |
JPX |
1-254651 |
Oct 1989 |
JPX |
5-201882 |
Aug 1993 |
JPX |
WO9507928 |
Mar 1995 |
WOX |
Non-Patent Literature Citations (1)
Entry |
International Search Report for International Appln. No. PCT/JP93/01909 mailed April 12, 1994. |
Divisions (1)
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Number |
Date |
Country |
Parent |
295649 |
Aug 1994 |
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