Methanol → (S)-N-[[3-(3-Fluorophenyl)-2-oxo-5-oxazolidinyl]methyl]acetamide

HRID 8523

反応式

HRID 8523 の反応式
CC(C)COC(=O)[NH:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([F:13])[CH:8]=1.[C:16]([O:19][C@H:20]([CH2:26]Cl)[CH2:21][NH:22][C:23](=[O:25])[CH3:24])(=[O:18])C.CO.[Cl-].[NH4+]>CCCCCCC.C1(C)C=CC=CC=1.O.CN(C)C=O>[F:13][C:9]1[CH:8]=[C:7]([N:6]2[CH2:26][C@H:20]([CH2:21][NH:22][C:23](=[O:25])[CH3:24])[O:19][C:16]2=[O:18])[CH:12]=[CH:11][CH:10]=1

参加物

9

反応物 4

HCID 887MethanolHCID 25517Ammonium ChlorideHCID 7357675(2S)-1-Acetamido-3-chloropropan-2-yl acetateHCID 159082813-Fluorophenylcarbamic acid 2-methylpropyl ester

生成物 1

HCID 11345751(S)-N-[[3-(3-Fluorophenyl)-2-oxo-5-oxazolidinyl]methyl]acetamide収率 63%

試薬・触媒・溶媒 4

HCID 962Water溶媒HCID 1140Toluene溶媒HCID 6228Dimethylformamide溶媒HCID 8900Heptane溶媒2 回

反応条件

温度
1.5 °C

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%).

後処理

  1. temperaturewhile maintaining 8 to 10° C
  2. washThe reaction mixture is rinsed in with a mixture of water (100 ml), saturated ammonium chloride (50 ml) and toluene (100 ml)
  3. filtrationThe precipitate is collected by vacuum filtration
  4. washwashed with heptane (1 liter) and water (1 liter)
  5. customdried in a nitrogen stream
  6. customto give 252.4 g of crude product
  7. customThis is triturated in acetonitrile (1 kg) at 90° C.
  8. concentrationthe slurry concentrated under reduced pressure to 800 ml total volume
  9. additionToluene (1900 ml) is added
  10. concentrationwhile concentrating
  11. temperatureto maintain 800 ml total volume
  12. additionWater (1 liter) and heptane (1 liter) are added
  13. filtrationthe precipitate collected by vacuum filtration
  14. washwashed with water (750 ml) and heptane (250 ml)
  15. customdried in a nitrogen stream

出典と根拠

ORDレコード
ord-f67a0952f0d348859053f3c20b62f4a3
出典データセット
uspto-grants-2006_08
特許番号
US07087784B2

関連ノート

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