4-Toluenesulfonyl chloride → Zofenopril Impurity 4

HRID 1245043

反応式

HRID 1245043 の反応式
C(N(CC)CC)C.[C:8]1([CH3:18])[CH:13]=[CH:12][C:11]([S:14](Cl)(=[O:16])=[O:15])=[CH:10][CH:9]=1.[CH3:19][O:20][C:21](=[O:38])[C@@H:22]1[CH2:26][C@@H:25]([OH:27])[CH2:24][N:23]1[C:28]([O:30][CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)=[O:29]>CN(C)C1C=CN=CC=1.C(Cl)Cl>[CH3:19][O:20][C:21](=[O:38])[C@@H:22]1[CH2:26][C@@H:25]([O:27][S:14]([C:11]2[CH:12]=[CH:13][C:8]([CH3:18])=[CH:9][CH:10]=2)(=[O:16])=[O:15])[CH2:24][N:23]1[C:28]([O:30][CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)=[O:29]

参加物

6

反応物 3

HCID 73974-Toluenesulfonyl chlorideHCID 8471TriethylamineHCID 6884112-Methyl 1-(phenylmethyl) (2S,4R)-4-hydroxy-1,2-pyrrolidinedicarboxylate

生成物 1

HCID 391525Zofenopril Impurity 4収率 100%

試薬・触媒・溶媒 2

HCID 142844-(Dimethylamino)pyridine触媒HCID 6344Dichloromethane溶媒

実験手順

37.5 ml (270 mmol) of triethylamine, 49.04 g (257 mmol) of p-toluenesulfonyl chloride and 2.99 g (24.5 mmol) of 4-dimethylaminopyridine were added in turn to a solution of 77.70 g (245 mmol) of (2S,4R)-1-benzyloxycarbonyl-4-hydroxyproline methyl ester in 600 ml of methylene chloride, and the resulting mixture was then stirred at room temperature overnight. At the end of this time, the reaction mixture was concentrated by evaporation under reduced pressure and the residue was partitioned between ethyl acetate and water. The organic extract was washed with water, dried over anhydrous magnesium sulfate and then concentrated by evaporation under reduced pressure. The resulting residue was purified by chromatography on a silica gel column using a 1:1 by volume mixture of hexane and ethyl acetate as the eluant to afford 106.18 g (quantitative yield) of (2S,4R)-1-benzyloxycarbonyl-4-(p-toluenesulfonyloxy)proline methyl ester as a yellow oil.

後処理

  1. concentrationAt the end of this time, the reaction mixture was concentrated by evaporation under reduced pressure
  2. customthe residue was partitioned between ethyl acetate and water
  3. extractionThe organic extract
  4. washwas washed with water
  5. dry with materialdried over anhydrous magnesium sulfate
  6. concentrationconcentrated by evaporation under reduced pressure
  7. customThe resulting residue was purified by chromatography on a silica gel column
  8. additionby volume mixture of hexane and ethyl acetate as the eluant

出典と根拠

ORDレコード
ord-2a2767bd6d844d609c55954f11dad087
出典データセット
uspto-grants-2006_10
特許番号
US07122666B2

関連ノート

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