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

HRID 417195ノート

反応式

HRID 417195 の反応式
C([Si](C)(C)O[CH2:7][CH2:8][N:9]1[CH:14]=[CH:13][C:12]([NH:15][C:16]([CH:18]2[NH:22][CH:21]([CH2:23][C:24]([CH3:27])([CH3:26])[CH3:25])[C:20]3([C:35]4[C:30](=[CH:31][C:32]([Cl:36])=[CH:33][CH:34]=4)[NH:29][C:28]3=[O:37])[CH:19]2[C:38]2[CH:43]=[CH:42][CH:41]=[C:40]([Cl:44])[C:39]=2[F:45])=[O:17])=[CH:11][C:10]1=[O:46])(C)(C)C.Cl.O1CCC[CH2:51]1>>[O:46]=[C:10]1[CH:11]=[C:12]([NH:15][C:16]([CH:18]2[NH:22][CH:21]([CH2:23][C:24]([CH3:27])([CH3:25])[CH3:26])[C:20]3([C:35]4[C:30](=[CH:31][C:32]([Cl:36])=[CH:33][CH:34]=4)[NH:29][C:28]3=[O:37])[CH:19]2[C:38]2[CH:43]=[CH:42][CH:41]=[C:40]([Cl:44])[C:39]=2[F:45])=[O:17])[CH:13]=[CH:14][N:9]1[CH2:8][CH2:7][CH3:51]

参加物

4

反応物 3

HCID 313Hydrochloric AcidHCID 8028TetrahydrofuranHCID 76741121rac-(2'S,3'R,4'S,5'R)-6-chloro-4'-(3-chloro-2-fluoro-phenyl)-2'-(2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro[indole-3,3'-pyrrolidine]-5'-carboxylic acid {1-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-2-oxo-1,2-dihydro-pyridin-4-yl}-amide

生成物 1

HCID 77154983rac-(2'S,3'R,4'S,5'R)-6-chloro-4'-(3-chloro-2-fluoro-phenyl)-2'-(2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro[indole-3,3'-pyrrolidine]-5'-carboxylic acid (2-oxo-1-propyl-1,2-dihydro-pyridin-4-yl)-amide

実験手順

To a solution of rac-(2′S,3′R,4′S,5′R)-6-chloro-4′-(3-chloro-2-fluoro-phenyl)-2′-(2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro[indole-3,3′-pyrrolidine]-5′-carboxylic acid {1-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-2-oxo-1,2-dihydro-pyridin-4-yl}-amide (0.1 g, 0.14 mmol) in tetrahydrofuran (3 mL) was added aqueous HCl solution (1N, 3 mL, 3 mmol). The reaction mixture was stirred at room temperature for 1 h. The mixture was concentrated. The residue was partitioned between ethyl acetate and aqueous saturated NaHCO3 solution. The organic layer was separated, washed with water, brine, dried over Na2SO4, then concentrated. The residue was purified by chromatography (10-15% of MeOH in EtOAc) to give rac-(2′S,3′R,4′S,5′R)-6-chloro-4′-(3-chloro-2-fluoro-phenyl)-2′-(2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro[indole-3,3′-pyrrolidine]-5′-carboxylic acid (2-oxo-1-propyl-1,2-dihydro-pyridin-4-yl)-amide as a white solid (Yield, 12 mg, 14%).

後処理

  1. concentrationThe mixture was concentrated
  2. customThe residue was partitioned between ethyl acetate and aqueous saturated NaHCO3 solution
  3. customThe organic layer was separated
  4. washwashed with water, brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated
  7. customThe residue was purified by chromatography (10-15% of MeOH in EtOAc)
  8. customto give

出典と根拠

ORDレコード
ord-350cae2ac52344e498190e6219666499
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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