Morpholine → N-[[3-[3-fluoro-4-[4-[3-(4-morpholinyl)-1-oxopropyl]-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide

HRID 1078531

反応式

HRID 1078531 の反応式
[N:1]1([CH2:7][CH2:8][C:9]([OH:11])=O)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.N1CCOCC1.C(OCC)(=O)C=C.C1(N=C=NC2CCCCC2)CCCCC1.[F:40][C:41]1[CH:42]=[C:43]([N:53]2[CH2:57][C@H:56]([CH2:58][NH:59][C:60](=[O:62])[CH3:61])[O:55][C:54]2=[O:63])[CH:44]=[CH:45][C:46]=1[N:47]1[CH2:52][CH2:51][NH:50][CH2:49][CH2:48]1>CN(C)C1C=CN=CC=1.O1CCCC1.ClCCl.C(O)C>[F:40][C:41]1[CH:42]=[C:43]([N:53]2[CH2:57][CH:56]([CH2:58][NH:59][C:60](=[O:62])[CH3:61])[O:55][C:54]2=[O:63])[CH:44]=[CH:45][C:46]=1[N:47]1[CH2:52][CH2:51][N:50]([C:9](=[O:11])[CH2:8][CH2:7][N:1]2[CH2:2][CH2:3][O:4][CH2:5][CH2:6]2)[CH2:49][CH2:48]1

参加物

9

反応物 5

HCID 8083MorpholineHCID 8821Ethyl AcrylateHCID 10868DicyclohexylcarbodiimideHCID 4108133-(Morpholin-4-yl)propanoic acidHCID 10520848(S)-N-((3-(3-fluoro-4-(piperazin-1-yl)phenyl)-2-oxooxazolidin-5-yl)methyl)acetamide

生成物 1

HCID 21462637N-[[3-[3-fluoro-4-[4-[3-(4-morpholinyl)-1-oxopropyl]-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide収率 95%

試薬・触媒・溶媒 3

HCID 142844-(Dimethylamino)pyridine触媒HCID 702Ethanol溶媒HCID 21919333Tetrahydrofurane dichloromethane溶媒

実験手順

3-(4-Morpholinyl)propionic acid (0.600 g, 2.11 mmol), prepared by condensation of morpholine with ethyl acrylate (3 equivalents) in refluxing ethanol, followed by distillation, saponification (1N aqueous sodium hydroxide, tetrahydrofuran, reflux), neutralization (1N HCl) and lyophilization, was combined with 1,3-dicyclohexylcarbodiimide (0.434 g, 2.11 mmol), 4-(dimethylamino)pyridine (13 mg, 0.11 mmol), (S)-N-[[3-[3-fluoro-4-(1-piperazinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide (0.354 g, 1.05 mmol), and 1:1 tetrahydrofuran/dichloromethane (50 mL) at room temperature. After 3 days the reaction mixture was filtered to remove the precipitated 1,3-dicyclohexylurea and the filtrate concentrated in vacuo. The crude product was chromatographed over silica gel (20 g), eluting with a gradient of 1-6% methanol/chloroform, to give 0.446 g (95%) of the title compound as a white solid with mp 209°-210° C. ##STR12##

後処理

  1. distillationfollowed by distillation, saponification (1N aqueous sodium hydroxide, tetrahydrofuran, reflux), neutralization (1N HCl) and lyophilization
  2. filtrationAfter 3 days the reaction mixture was filtered
  3. customto remove the precipitated 1,3-dicyclohexylurea
  4. concentrationthe filtrate concentrated in vacuo
  5. customThe crude product was chromatographed over silica gel (20 g)
  6. washeluting with a gradient of 1-6% methanol/chloroform

出典と根拠

ORDレコード
ord-aa7de4649cc44da494795db35a686cc8
出典データセット
uspto-grants-1996_08
特許番号
US05547950

関連ノート

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