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

HRID 417260ノート

反応式

HRID 417260 の反応式
[Cl:1][C:2]1[CH:7]=[C:6]2[NH:8][C:9](=[O:43])[C@:10]3([C@@H:14]([C:15]4[CH:20]=[CH:19][CH:18]=[C:17]([Cl:21])[C:16]=4[F:22])[C@H:13]([C:23](=[O:33])[NH:24][C:25]4[CH:30]=[CH:29][C:28]([C:31]#[N:32])=[CH:27][CH:26]=4)[NH:12][C@H:11]3[CH2:34][C:35]([CH3:42])([CH3:41])[CH2:36][O:37]C(=O)C)[C:5]2=[CH:4][CH:3]=1.[OH-].[Na+].CO>O1CCCC1>[C:31]([C:28]1[CH:27]=[CH:26][C:25]([NH:24][C:23]([CH:13]2[NH:12][CH:11]([CH2:34][C:35]([CH3:42])([CH3:41])[CH2:36][OH:37])[C:10]3([C:5]4[C:6](=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=4)[NH:8][C:9]3=[O:43])[CH:14]2[C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([Cl:21])[C:16]=2[F:22])=[O:33])=[CH:30][CH:29]=1)#[N:32]

参加物

5

反応物 3

HCID 887MethanolHCID 14798Sodium HydroxideHCID 53239123acetic acid rac-3-[(2'S,3'R,4'S,5'R)-6-chloro-4'-(3-chloro-2-fluoro-phenyl)-5'-(4-cyano-phenylcarbamoyl)-2-oxo-1,2-dihydro-spiro[indole-3,3'-pyrrolidin]-2'-yl]-2,2-dimethyl-propyl ester

生成物 1

HCID 75986479rac-(2'S,3'R,4'S,5'R)-6-chloro-4'-(3-chloro-2-fluoro-phenyl)-2'-(3-hydroxy-2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro[indole-3,3'-pyrrolidine]-5'-carboxylic acid (4-cyano-phenyl)-amide

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

To a solution of acetic acid rac-3-[(2′S,3′R,4′S,5′R)-6-chloro-4′-(3-chloro-2-fluoro-phenyl)-5′-(4-cyano-phenylcarbamoyl)-2-oxo-1,2-dihydro-spiro[indole-3,3′-pyrrolidin]-2′-yl]-2,2-dimethyl-propyl ester (17 mg, 0.027 mmol) in tetrahydrofuran (2 mL) was added an aqueous solution (1N) of NaOH (0.5 mL, 0.5 mmol) and methanol (0.2 mL). The reaction mixture was stirred at room temperature for 18 h. The mixture was concentrated, and the residue was partitioned between ethyl acetate and water. The organic layer was separated, and the aqueous layer was extracted with ethyl acetate twice. The organic extracts were combined, washed with water, brine, dried over MgSO4, and concentrated to give rac-(2′S,3′R,4′S,5′R)-6-chloro-4′-(3-chloro-2-fluoro-phenyl)-2′-(3-hydroxy-2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro[indole-3,3′-pyrrolidine]-5′-carboxylic acid (4-cyano-phenyl)-amide as a off white solid (14 mg, 88%).

後処理

  1. concentrationThe mixture was concentrated
  2. customthe residue was partitioned between ethyl acetate and water
  3. customThe organic layer was separated
  4. extractionthe aqueous layer was extracted with ethyl acetate twice
  5. washwashed with water, brine
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated

出典と根拠

ORDレコード
ord-9f530a4f897a4ffab7dcd77d08c3b3c5
出典データセット
uspto-grants-2012_01
特許番号
US08088815B2

反応ノート

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