Water → rac-(2'S,3'S,4'S)-6-chloro-2'-(3-chloro-2-fluoro-phenyl)-4'-(2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro[indole-3,3'-pyrrolidine]-1'-carboxylic acid 4-methoxycarbonyl-phenyl ester

HRID 2065429ノート

反応式

HRID 2065429 の反応式
[OH:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][CH:3]=1.[H-].[Na+].[Cl:14][C:15]1[CH:20]=[C:19]2[NH:21][C:22](=[O:44])[C:23]3([CH:27]([CH2:28][C:29]([CH3:32])([CH3:31])[CH3:30])[CH2:26][N:25]([C:33](Cl)=[O:34])[CH:24]3[C:36]3[CH:41]=[CH:40][CH:39]=[C:38]([Cl:42])[C:37]=3[F:43])[C:18]2=[CH:17][CH:16]=1.O>CN(C)C=O>[CH3:9][O:8][C:6]([C:5]1[CH:4]=[CH:3][C:2]([O:1][C:33]([N:25]2[CH2:26][CH:27]([CH2:28][C:29]([CH3:32])([CH3:31])[CH3:30])[C:23]3([C:18]4[C:19](=[CH:20][C:15]([Cl:14])=[CH:16][CH:17]=4)[NH:21][C:22]3=[O:44])[CH:24]2[C:36]2[CH:41]=[CH:40][CH:39]=[C:38]([Cl:42])[C:37]=2[F:43])=[O:34])=[CH:11][CH:10]=1)=[O:7]

参加物

6

反応物 4

HCID 962WaterHCID 7456MethylparabenHCID 24758Sodium hydrideHCID 76776161rac-(2'S,3'S,4'S)-6-chloro-2'-(3-chloro-2-fluoro-phenyl)-4'-(2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro[indole-3,3'-pyrrolidine]-1'-carbonyl chloride

生成物 1

HCID 67337314rac-(2'S,3'S,4'S)-6-chloro-2'-(3-chloro-2-fluoro-phenyl)-4'-(2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro[indole-3,3'-pyrrolidine]-1'-carboxylic acid 4-methoxycarbonyl-phenyl ester収率 18%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

To a solution of methyl 4-hydroxybenzoate (Aldrich) (20 mg, 0.13 mmol) in N,N-dimethylforamide (3 mL) was added NaH (60%, 7.8 mg, 0.2 mmol). The reaction mixture was stirred at room temperature for 10 min, then rac-(2′S,3′S,4′S)-6-chloro-2′-(3-chloro-2-fluoro-phenyl)-4′-(2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro[indole-3,3′-pyrrolidine]-1′-carbonyl chloride prepared in Example 8 (56 mg, 0.13 mmol) was added. The reaction mixture was stirred at room temperature for 3 h. Water was added. The mixture was partitioned between ethyl acetate and water. The organic layer was separated, and the aqueous layer was extracted with ethyl acetate. The organic layers were combined, washed with water, brine, dried over MgSO4, and concentrated. The residue was triturated with dichloromethane and hexanes to give rac-(2′S,3′S,4′S)-6-chloro-2′-(3-chloro-2-fluoro-phenyl)-4′-(2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro[indole-3,3′-pyrrolidine]-1′-carboxylic acid 4-methoxycarbonyl-phenyl ester as a white solid (Yield 14 mg, 18%).

後処理

  1. stirringThe reaction mixture was stirred at room temperature for 3 h
  2. customThe mixture was partitioned between ethyl acetate and water
  3. customThe organic layer was separated
  4. extractionthe aqueous layer was extracted with ethyl acetate
  5. washwashed with water, brine
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated
  8. customThe residue was triturated with dichloromethane and hexanes

出典と根拠

ORDレコード
ord-c7aa36c23bc94c03828c267be0c2c3d1
出典データセット
uspto-grants-2012_10
特許番号
US08288431B2

反応ノート

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