5(R)-(N-(2,2,2-Trichloroethyloxycarbonyl)-isoxazol-3-ylaminomethyl)-3-(4-imidazol-1-yl-3-fluorophenyl)oxazolidin-2-one → (5S)-3-(3-fluoro-4-imidazol-1-yl-phenyl)-5-[(isoxazol-3-ylamino)methyl]oxazolidin-2-one

HRID 1582332

反応式

HRID 1582332 の反応式
ClC(Cl)(Cl)COC([N:7]([CH2:13][C@@H:14]1[O:18][C:17](=[O:19])[N:16]([C:20]2[CH:25]=[CH:24][C:23]([N:26]3[CH:30]=[CH:29][N:28]=[CH:27]3)=[C:22]([F:31])[CH:21]=2)[CH2:15]1)[C:8]1[CH:12]=[CH:11][O:10][N:9]=1)=O>C(O)(=O)C.O.[Zn]>[O:10]1[CH:11]=[CH:12][C:8]([NH:7][CH2:13][C@@H:14]2[O:18][C:17](=[O:19])[N:16]([C:20]3[CH:25]=[CH:24][C:23]([N:26]4[CH:30]=[CH:29][N:28]=[CH:27]4)=[C:22]([F:31])[CH:21]=3)[CH2:15]2)=[N:9]1

参加物

5

反応物 1

HCID 571687335(R)-(N-(2,2,2-Trichloroethyloxycarbonyl)-isoxazol-3-ylaminomethyl)-3-(4-imidazol-1-yl-3-fluorophenyl)oxazolidin-2-one

生成物 1

HCID 497417(5S)-3-(3-fluoro-4-imidazol-1-yl-phenyl)-5-[(isoxazol-3-ylamino)methyl]oxazolidin-2-one収率 41.8%

試薬・触媒・溶媒 3

HCID 23994Zinc触媒2 回HCID 176Acetic Acid溶媒HCID 962Water溶媒

実験手順

5(R)-(N-(2,2,2-Trichloroethyloxycarbonyl)-isoxazol-3-ylaminomethyl)-3-(4-imidazol-1-yl-3-fluorophenyl)oxazolidin-2-one (crude, 1.7 g, ˜2.5 mM), was stirred in a mixture of acetic acid (40 ml) and water (18 ml) under nitrogen at ambient temperature. Zinc dust (824 mg, 12.5 mM) was added, the mixture stirred 20 minutes, a further portion (200 mg ) of zinc added, and stirring continued for 1 hour. The mixture was filtered through celite, and the filter pad washed well with a mixture of acetic acid and water (5:1). The filtrates were evaporated, and the residue partitioned between hydrochloric acid (0.5 M, 200 ml) and dichloromethane (150 ml). The aqueous phase was washed with dichloromethane (100 ml), then made basic with the minimum quantity of concentrated ammonia solution, re-extracted with dichloromethane (2×150 ml), dried (magnesium sulfate), and evaporated. Recrystallisation from isopropanol (40 ml) gave the desired product (470 mg ). NMR (DMSO-d6) δ: 3.46 (t, 2H); 3.87 (dd, 1H); 4.21 (t, 1H); 4.92 (m, 1H); 6.01 (d, 1H); 6.53 (t, 1H); 7.12 (t, 1H); 7.46 (dd, 1H); 7.53 (d, 1H); 7.66 (t, 1H); 7.74 (dd, 1H); 7.98 (m, 1H); 8.39 (d, 1H). MS (ESP): 362 (MH+) for C16H14FN5O3

後処理

  1. stirringstirring
  2. waitcontinued for 1 hour
  3. filtrationThe mixture was filtered through celite
  4. washthe filter pad washed well with a mixture of acetic acid and water (5:1)
  5. customThe filtrates were evaporated
  6. customthe residue partitioned between hydrochloric acid (0.5 M, 200 ml) and dichloromethane (150 ml)
  7. washThe aqueous phase was washed with dichloromethane (100 ml)
  8. extractionre-extracted with dichloromethane (2×150 ml)
  9. dry with materialdried (magnesium sulfate)
  10. customevaporated
  11. customRecrystallisation from isopropanol (40 ml)

出典と根拠

ORDレコード
ord-2e13352ce45b4901b2f937897b1b0cec
出典データセット
uspto-grants-2004_05
特許番号
US06734200B1

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