反応 #8619

反応方程式

3-fluorophenylcarbamic acid 2-methylpropyl ester

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

methanol

ammonium chloride

→

title compound

収率 63.0%

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

収率 63.0%

溶媒

heptane

N,N-dimethylformamide

heptane

toluene

water

反応条件

後処理

1. 1
   温度while maintaining 8 to 10° C
2. 2
   洗浄The reaction mixture is rinsed in with a mixture of water (100 ml), saturated ammonium chloride (50 ml) and toluene (100 ml)
3. 3
   ろ過The precipitate is collected by vacuum filtration
4. 4
   洗浄washed with heptane (1 liter) and water (1 liter)
5. 5
   その他dried in a nitrogen stream
6. 6
   その他to give 252.4 g of crude product
7. 7
   その他This is triturated in acetonitrile (1 kg) at 90° C.
8. 8
   濃縮the slurry concentrated under reduced pressure to 800 ml total volume
9. 9
   workup.ADDITIONToluene (1900 ml) is added
10. 10
    濃縮while concentrating
11. 11
    温度to maintain 800 ml total volume
12. 12
    workup.ADDITIONWater (1 liter) and heptane (1 liter) are added
13. 13
    ろ過the precipitate collected by vacuum filtration
14. 14
    洗浄washed with water (750 ml) and heptane (250 ml)
15. 15
    その他dried in a nitrogen stream

実験手順

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%).

出典