Hydrogen Peroxide → rac-(2'S,3'R,4'S,5'R)-6-chloro-4'-(3-chloro-2-fluoro-phenyl)-2'-(2,2-dimethyl-propyl)-5-fluoro-2-oxo-1,2-dihydro-spiro[indole-3,3'-pyrrolidine]-5'-carboxylic acid (4-carbamoyl-2-methoxy-phenyl)-amide

HRID 417267ノート

反応式

HRID 417267 の反応式
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10]([CH:12]2[NH:16][CH:15]([CH2:17][C:18]([CH3:21])([CH3:20])[CH3:19])[C:14]3([C:29]4[C:24](=[CH:25][C:26]([Cl:31])=[C:27]([F:30])[CH:28]=4)[NH:23][C:22]3=[O:32])[CH:13]2[C:33]2[CH:38]=[CH:37][CH:36]=[C:35]([Cl:39])[C:34]=2[F:40])=[O:11])=[C:5]([O:41][CH3:42])[CH:4]=1)#[N:2].[OH:43]O.[OH-].[Na+]>CS(C)=O>[C:1]([C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10]([CH:12]2[NH:16][CH:15]([CH2:17][C:18]([CH3:21])([CH3:20])[CH3:19])[C:14]3([C:29]4[C:24](=[CH:25][C:26]([Cl:31])=[C:27]([F:30])[CH:28]=4)[NH:23][C:22]3=[O:32])[CH:13]2[C:33]2[CH:38]=[CH:37][CH:36]=[C:35]([Cl:39])[C:34]=2[F:40])=[O:11])=[C:5]([O:41][CH3:42])[CH:4]=1)(=[O:43])[NH2:2]

参加物

5

反応物 3

HCID 784Hydrogen PeroxideHCID 14798Sodium HydroxideHCID 75986555rac-(2'S,3'R,4'S,5'R)-6-chloro-4'-(3-chloro-2-fluoro-phenyl)-2'-(2,2-dimethyl-propyl)-5-fluoro-2-oxo-1,2-dihydro-spiro[indole-3,3'-pyrrolidine]-5'-carboxylic acid (4-cyano-2-methoxy-phenyl)-amide

生成物 1

HCID 75986556rac-(2'S,3'R,4'S,5'R)-6-chloro-4'-(3-chloro-2-fluoro-phenyl)-2'-(2,2-dimethyl-propyl)-5-fluoro-2-oxo-1,2-dihydro-spiro[indole-3,3'-pyrrolidine]-5'-carboxylic acid (4-carbamoyl-2-methoxy-phenyl)-amide収率 72%

試薬・触媒・溶媒 1

HCID 679Dimethyl Sulfoxide溶媒

反応条件

温度
10 °C

実験手順

To the solution of rac-(2′S,3′R,4′S,5′R)-6-chloro-4′-(3-chloro-2-fluoro-phenyl)-2′-(2,2-dimethyl-propyl)-5-fluoro-2-oxo-1,2-dihydro-spiro[indole-3,3′-pyrrolidine]-5′-carboxylic acid (4-cyano-2-methoxy-phenyl)-amide (0.23 g, 0.38 mmol) prepared in Example 112 in DMSO (2 mL) at 0° C. was added an aqueous solution (30% Aldrich) of H2O2 (0.64 g, 5.6 mmol), then aqueous solution (1N) of NaOH (1.9 mL, 1.9 mmol) was added dropwise. The reaction mixture was stirred at 10° C. for 1 h. The mixture was partitioned between ethyl acetate and saturated aqueous Na2SO3 solution. The organic layer was separated, washed with water, brine, dried over MgSO4, and concentrated. The residue was triturated with dichloromethane and hexanes to give rac-(2′S,3′R,4′S,5′R)-6-chloro-4′-(3-chloro-2-fluoro-phenyl)-2′-(2,2-dimethyl-propyl)-5-fluoro-2-oxo-1,2-dihydro-spiro[indole-3,3′-pyrrolidine]-5′-carboxylic acid (4-carbamoyl-2-methoxy-phenyl)-amide as a white solid (Yield 0.17 g, 72%)

後処理

  1. customThe mixture was partitioned between ethyl acetate and saturated aqueous Na2SO3 solution
  2. customThe organic layer was separated
  3. washwashed with water, brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated
  6. customThe residue was triturated with dichloromethane and hexanes

出典と根拠

ORDレコード
ord-1e9927d7e39c454999157b21b946859e
出典データセット
uspto-grants-2012_01
特許番号
US08088815B2

反応ノート

読み込み中…