Patent EA-004434-B1 (EA)
Title: Linezolid-crystal form ii
Inventor: BERGREN MICHAEL S
IPC: C07D413/10
Filed: 2001-01-29
Abstract: 1. (S)-N-[[3-[3-fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl) methyl] acetamide, crystal "Form II" with a powder X-ray diffraction spectrum of: d-spacing ( angstrom )  Two-Theta Angle ( degree)  Relative Intensity (%) 12.44  7.10  2 9.26  9.56.37  13.88  6 6.22  14.23  24 5.48  16.18  3 5.28  100 5.01  17.69  2 4.57  19.41  4 4.50  19.69  29.93  6 4.11  21.61  15 3.97  22.39  23 3.89  22.878  23.52  7 3.68  24.16  1 3.52  25.28  13 3.34   3.30  27.01  3 3.21  27.77  1 2. (S)-N-[[3-[3-flu4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl] acetamide, crystal "Form II" with an infrared (IR) spectrum as a mineral oil mull: 3364, 1748, 1675, 1537, 1517, 1445, 1410, 1401, 1358, 1329, 1287, 1274, 1253, 1237, 1221, 1145, 1130, 1123, 1116, 1078, 1066, 1049, 907, 852 and 758 cm <-1>. 3. A process to prepare (S)-N-[[3-[3-fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide, crystal "Form II" which comprises: (1) producing: (S)-N-[[3-[3-fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-xazolidinyl]methyl]acetamide in greater than 98% enantiomeric purity, (2) mixing the greater than 98% enantiomerically pure (S)-N-[[3-[3-fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide in a solvent or mixture of solvents at a temperature below a temperature of about 80 degree and (3) separating the (S)-N-[[3-[3-fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide crystal "Form II" from the solvent(s). 4. A process according to claim 3 where the enantiomeric purity is greater than 99%. 5. A process according to claim 4 where the enantiomeric purity is greater than 99.5%. 6. A process according to claim 3 where the solvent is selected from the group consisting of compounds of the formula: water, acetonitrile, chloroform, methylene chloride, toluene, R1-OH where R1 is C1-C6 alkyl, R1-CO-R2 where R2 is C1-C6 alkyl or phenyl substituted with 1 thru 3 R1 where R1 is as defined above, and where R1 is as defined above, R1-CO-O-R2 where R1 is C1-C6 alkyl and R1 is as defined above, R1-O-R2 where R1 is C1-C6 alkyl and R1 is as defined above. 7. A process according to claim 6 where the solvent is selected from the group consisting of water, ethyl acetate, methanol, ethanol, propanol, i-propanol, butanol, acetonitrile, acetone, methyl ethyl ketone, chloroform, methylene chloride, toluene, xylene, diethyl ether, or methyl-t-butyl ether. 8. A process according to claim 6 where the solvent is selected from the group consisting of ethyl acetate, acetone, acetonitrile, propanol, or isopropanol. 9. A process according to claim 6 where the solvent is ethyl acetate. 10. A process according to claim 3 where the (S)-N-([3-[3-fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide is mixed for at least 10 min in the solvent or mixture of solvents. 11. A process according to claim 10 where the (S)-N-[[3-[3-fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide is mixed for at least 20 min in the solvent or mixture of solvents. 12. A process according to claim 10 where the linezolid is mixed for at least 30 min in the solvent or mixture of solvents. 13. A process according to claim 3 where the temperature is less than about 75 degree . 14. A process according to claim 10 where the temperature is from about 45 degree to about 60 degree . 15. A process according to claim 3 where the (S)-N-[[3-[3-fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide is isolated as a solid before mixing with a solvent or mixture of solvents. 16. A process according to claim 3 where the (S)-N-[[3-[3-fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide is kept in solution before mixing with a solvent or mixture of solvents.