LinezolidImpurity36 synthesis

Yield:1345879-85-7 100%

Reaction Conditions:

with potassium carbonate in methanol; for 2 h;Product distribution / selectivity;

Steps:

31

EXAMPLE 31. Scale-up of synthesis of (S) (E, Z)-N-4-chlorobenzylidene-l- (oxiran-2-yl)methanamine (16). (S) (E,Z)-l-(4-Chlorobenzylideneamino)-3-chloropropan-2- ol (18) (163 g, 0.7 mol), reagent grade methanol (1.5 L) and anhydrous K₂C0₃ (193 g, 1.4 mol) were added to a 3 L 3 neck round bottom flask with overhead stirrer. The reaction mixture was stirred vigorously. After 2 hrs GCMS showed complete conversion to the epoxide (small aliquot removed from the reaction, diluted with an equal volume of CH₃CN, filtered through disposable pipette with a cotton plug). The colorless reaction was diluted with CH₂CI₂ (1 L), brine (800 ml) and water (200 ml). The aqueous layer was extracted with additional CH₂CI₂ (250 ml). The combined organic layers were washed with brine (4 x 200 ml), dried (MgS0₄) and evaporated (bath temp 45 °C) to a colorless oil (136g, quantitative); 1H NMR (500 MHz, DMSO-d₆) δ 8.35 (s, 1H), 7.78 (d, 2H, J=8.2 Hz) ), 7.53 (d, 2H, J=8.2 Hz), 3.89 (ddd, 1H, J=13 Hz, J=3.5 Hz, J= 1.6 Hz), 3.55(ddd, 1H, J= 13 Hz, J= 6.1 Hz, J= 1.3 Hz), 3.25 (br ddd, 1H, J= 6.5 Hz, J=3.5Hz, J=2.8 Hz), 2.65 (dd, 1H, J= 5 Jz, J= 2.6 Hz), 2.77 (dd, 1H, J= 5Hz, J= 4.1 Hz); GCMS Retention time 8.98 min (m/e 194).

References:

WO2011/137222,2011,A1 Location in patent:Example 31