(S)-3,3,3-trifluoro-2-trimethylsilyloxy-2-methylpropanoyl chloride → (R)-N-(3-Acetamido-2-Chloro-4-{4-fluorophenylsulphanyl}phenyl)-2-hydroxy-2-methyl-3,3,3-trifluoropropanamide

HRID 2120354ノート

反応式

HRID 2120354 の反応式
[F:1][C:2]([F:14])([F:13])[C@@:3]([O:8][Si](C)(C)C)([CH3:7])[C:4](Cl)=[O:5].[C:15]([NH:18][C:19]1[C:20]([Cl:34])=[C:21]([CH:23]=[CH:24][C:25]=1[S:26][C:27]1[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=1)[NH2:22])(=[O:17])[CH3:16]>C(Cl)Cl.C(N(CC)CC)C>[C:15]([NH:18][C:19]1[C:20]([Cl:34])=[C:21]([NH:22][C:4](=[O:5])[C@:3]([OH:8])([CH3:7])[C:2]([F:14])([F:13])[F:1])[CH:23]=[CH:24][C:25]=1[S:26][C:27]1[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=1)(=[O:17])[CH3:16]

参加物

5

反応物 2

HCID 10586677(S)-3,3,3-trifluoro-2-trimethylsilyloxy-2-methylpropanoyl chloride2 回HCID 234393893-Acetamido-2-chloro-4-(4-fluorophenylsulphanyl)aniline

生成物 1

HCID 69882903(R)-N-(3-Acetamido-2-Chloro-4-{4-fluorophenylsulphanyl}phenyl)-2-hydroxy-2-methyl-3,3,3-trifluoropropanamide収率 57.9%

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒3 回HCID 8471Triethylamine溶媒2 回

実験手順

A solution of (S)-3,3,3-trifluoro-2-(trimethylsilyloxy)-2-methylpropanoyl chloride (prepared from (R)-3,3,3-trifluoro-2-hydroxy-2-methylpropionic acid (Method 25) as described in J. Med. Chem., 1999, 42, 2741-2746) (1.179 g) in DCM (10 ml) was added dropwise to a stirred and ice-cooled suspension of 3-acetamido-2-chloro-4-(4-fluorophenylsulphanyl)aniline (Method 18) (1.315 g) in DCM (20 ml) and triethylamine (1.72 ml). The mixture was allowed to warm to ambient temperature overnight. More triethylamine (0.8 ml) followed by (S)-3,3,3-trifluoro-2-(trimethylsilyloxy)-2-methylpropanoyl chloride (0.6 g) in DCM (5 ml) was added. After a further 6 hours the mixture was concentrated by evaporation. MeOH (50 ml) and 2M aqueous HCl (5 ml) were added, the mixture was stirred overnight, and then diluted with water (20 ml). The MeOH was removed by evaporation and 2M aqueous HCl (30 ml) was added. The mixture was then extracted with ether (2×80 ml). The extracts were washed with brine then dried. Volatile material was removed by evaporation and the residue was purified by chromatography on a Biotage cartridge (40 g silica), eluting with 50% EtOAc/isohexane to give the title compound (1.104 g) as a foam. NMR: 1.6 (s, 3H), 2.05 (s, 3H), 7.0 (d, 1H), 7.26 (t, 2H), 7.38-7.48 (m, 2H), 7.8-7.9 (m, 2H), 9.76 (brs, 1H), 9.9 (brs, 1H); m/z: 449.

後処理

  1. temperatureice-cooled
  2. additionwas added
  3. concentrationAfter a further 6 hours the mixture was concentrated by evaporation
  4. additionMeOH (50 ml) and 2M aqueous HCl (5 ml) were added
  5. stirringthe mixture was stirred overnight
  6. additiondiluted with water (20 ml)
  7. customThe MeOH was removed by evaporation and 2M aqueous HCl (30 ml)
  8. additionwas added
  9. extractionThe mixture was then extracted with ether (2×80 ml)
  10. washThe extracts were washed with brine
  11. customthen dried
  12. customVolatile material was removed by evaporation
  13. customthe residue was purified by chromatography on a Biotage cartridge (40 g silica)
  14. washeluting with 50% EtOAc/isohexane

出典と根拠

ORDレコード
ord-feb6a8fd24a346fe8a3d5a4a3c2cedf1
出典データセット
uspto-grants-2004_02
特許番号
US06689909B1

反応ノート

読み込み中…