8
A. HALAMA ET AL.
cooled below 35 ꢀC. After that 3.3 kg of (S)-1-chloro-3-{[(4-chlorophenyl)methylene]ami-
no}propan-2-ol and 11.5 L dichloromethane were added. The suspension was stirred and
heated at 40-45 ꢀC for 22 hours, then cooled below 25 ꢀC, 34.0 L of water added, then vigor-
ous stirring followed for 30 min. The organic layer was separated and dried over sodium
sulfate. The mixture was heated to 40 ꢀC and filtered. Ethanol (30.0 L) was poured into the
filtrate and was distilled off under vacuum at 300-400 mbar and a bath temperature at
45 ꢀC. Ethanol (27.0 L) was poured into the concentrated residue, the mixture heated at
50 ꢀC for 15 minutes, then gradually cooled to 15 ꢀC and stirred for 1.5 hours. The precipi-
tated solid was collected by filtration, washed with cold ethanol (2x 4.0 L) and dried. A
nearly white powder was obtained (4.04 kg, yield 84%), m.p. 143-144 ꢀC, HPLC 99.3%,
25
optical purity 100.0%, [a]D ¼-101.9ꢀ (CH2Cl2). 1H NMR (CDCl3), d (ppm): 3.75 (m, 2H,
CH2); 3.88-3.99 (m, 2H, CH2); 4.00-4.09 (m, 2H, CH2); 4.09-4,21 (m, 2H, CH2); 4.34 (s,
2H, CH2); 4.97 (m, 1H, CH); 7.30-7.40 (m, 4H); 7.54-7.68 (m, 4H); 8.35 (m, 1H, CH).13C
NMR (CDCl3), d (ppm): 48.2; 49.7; 63.2; 64.1; 68.6; 71.8; 119.0; 126.1; 128.9; 129.5; 134.0;
137; 137.1; 137.3; 154.5;163.5; 166.7. MS (m/z): 414.1219 (M þ H)þ. The following com-
pounds (R/S)-11 were prepared in an analogous manner.
Preparation of 4-{4-[(R)-5-[(((4-chlorophenyl)methylene)amino)methyl]-2-oxo-1,3-
oxazolidin-3-yl]phenyl}-morpholin-3-one ((R)-11b))
Yield 73% off-white powder, m.p. 146-147 ꢀC, purity by HPLC 100%, optical purity by HPLC
25
100%, [a]D ¼ þ102.3ꢀ (CH2Cl2). NMR and MS spectra correspond to (S)-11 (X 5 Cl).
Preparation of 4-{4-[(S)-5-[(((4-fluororophenyl)methylene)amino)methyl]-2-oxo-1,3-
oxazolidin-3-yl]phenyl}-morpholin-3-one ((S)-11a))
Yield 78% off-white powder, m.p. 156-157 ꢀC, purity by HPLC 99.3%, optical purity by
25
1
HPLC 99.6%, [a]D ¼ -95.7ꢀ (CH2Cl2). H NMR (CDCl3), d(ppm): 3.75 (m, 2H, CH2);
3.88-3.99 (m, 2H, CH2); 4.03 (m, 2H, CH2); 4.09-4,19 (m, 2H, CH2); 4.34 (s, 2H, CH2);
4.97 (m, 1H, CH); 7.08 (m, 2H); 7.34 (m, 2H); 7.59 (m, 2H); 7.70 (m, 2H); 8.35 (m,
1H, CH).13C NMR (CDCl3), d(ppm): 48.1; 49.7; 63.1; 64.1; 68.5; 71.8; 115.7; 119.0;
126.1; 130.3; 131.8; 137.0; 154.5; 163.3; 163.6; 165.6; 166.7.
Preparation of 4-{4-[(R)-5-[(((4-fluororophenyl)methylene)amino)methyl]-2-oxo-1,3-
oxazolidin-3-yl]phenyl}-morpholin-3-one ((R)-11a))
Yield 68% off-white powder, m.p. 156.5-157.5 ꢀC, purity by HPLC 99.7%, optical purity
25
by HPLC 100%, [a]D ¼ þ95.2ꢀ (CH2Cl2). NMR spectra correspond to (S)-11a.
Preparation of 4-{4-[(S)-5-[(((4-bromophenyl)methylene)amino)methyl]-2-oxo-1,3-
oxazolidin-3-yl]phenyl}-morpholin-3-one ((S)-11c))
Yield 60% off-white powder, m.p. 150.5-151.5 ꢀC, purity by HPLC 100%, optical purity
25
1
by HPLC 100%, [a]D ¼ -95.6ꢀ (CH2Cl2). H NMR (CDCl3), d(ppm): 3.68 (m, 2H,
CH2); 3.81-3.91 (m, 2H, CH2); 3.96 (m, 2H, CH2); 4.02-4.12 (m, 2H, CH2); 4.27 (s, 2H,