Reaktion #8619

Reaktionsgleichung

3-fluorophenylcarbamic acid 2-methylpropyl ester

(S)—N-[2-(acetyloxy)-3-chloropropyl]acetamide

methanol

ammonium chloride

→

title compound

Ausbeute 63.0%

(S)—N-[[3-(3-fluorophenyl)-2-oxo-5-oxazolidinyl]methyl]acetamide

Ausbeute 63.0%

Lösungsmittel

heptane

N,N-dimethylformamide

heptane

toluene

water

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturwhile maintaining 8 to 10° C
2. 2
   WaschenThe reaction mixture is rinsed in with a mixture of water (100 ml), saturated ammonium chloride (50 ml) and toluene (100 ml)
3. 3
   FiltrationThe precipitate is collected by vacuum filtration
4. 4
   Waschenwashed with heptane (1 liter) and water (1 liter)
5. 5
   Sonstigedried in a nitrogen stream
6. 6
   Sonstigeto give 252.4 g of crude product
7. 7
   SonstigeThis is triturated in acetonitrile (1 kg) at 90° C.
8. 8
   Einengenthe slurry concentrated under reduced pressure to 800 ml total volume
9. 9
   workup.ADDITIONToluene (1900 ml) is added
10. 10
    Einengenwhile concentrating
11. 11
    Temperaturto maintain 800 ml total volume
12. 12
    workup.ADDITIONWater (1 liter) and heptane (1 liter) are added
13. 13
    Filtrationthe precipitate collected by vacuum filtration
14. 14
    Waschenwashed with water (750 ml) and heptane (250 ml)
15. 15
    Sonstigedried in a nitrogen stream

Vorschrift

To a mixture of 3-fluorophenylcarbamic acid 2-methylpropyl ester (300.0 g, 1.42 mol), (S)—N-[2-(acetyloxy)-3-chloropropyl]acetamide (556.1 g, 2.87 mol, 2.02 eq), methanol (90.03 g, 2.81 mol, 1.98 eq) and N,N-dimethylformamide (500 ml) is added a slurry of lithium t-amylate (401.3 g, 4.27 mol, 3.00 eq) in heptane (1 liter) while maintaining −4 to 7° C., followed by heptane (100 ml). The mixture is then stirred at 19 to 20° C. for 21 h. The reaction mixture is then added to a mixture of ammonium chloride (228 g, 4.26 mol, 3.00 eq), water (2.0 liter) and toluene (1.0 liter) while maintaining 8 to 10° C. The reaction mixture is rinsed in with a mixture of water (100 ml), saturated ammonium chloride (50 ml) and toluene (100 ml). The precipitate is collected by vacuum filtration and washed with heptane (1 liter) and water (1 liter) and dried in a nitrogen stream to give 252.4 g of crude product. This is triturated in acetonitrile (1 kg) at 90° C. and the slurry concentrated under reduced pressure to 800 ml total volume. Toluene (1900 ml) is added while concentrating to maintain 800 ml total volume. Water (1 liter) and heptane (1 liter) are added and the precipitate collected by vacuum filtration, washed with water (750 ml) and heptane (250 ml) and dried in a nitrogen stream to give the title compound (225.7 g, 63.0%).

Quelle