Trifluoroacetic acid → racemic (2'S,3S,4'R)-6-chloro-2'-(3-chlorophenyl)-4'-(5-fluoro-2-methyl-phenyl)-1'-hydroxycarbonylmethyl-spiro[3H-indole-3,3'-piperidine]-2,6'(1H)-dione

HRID 1728081ノート

反応式

HRID 1728081 の反応式
[Cl:1][C:2]1[CH:7]=[C:6]2[NH:8][C:9](=[O:40])[C:10]3([CH:15]([C:16]4[CH:21]=[C:20]([F:22])[CH:19]=[CH:18][C:17]=4[CH3:23])[CH2:14][C:13](=[O:24])[N:12]([CH2:25][C:26]([O:28]C(C)(C)C)=[O:27])[CH:11]3[C:33]3[CH:38]=[CH:37][CH:36]=[C:35]([Cl:39])[CH:34]=3)[C:5]2=[CH:4][CH:3]=1.COC([Si](C)(C)C)C.FC(F)(F)C(O)=O.CCN(C(C)C)C(C)C>ClCCl>[Cl:1][C:2]1[CH:7]=[C:6]2[NH:8][C:9](=[O:40])[C:10]3([CH:15]([C:16]4[CH:21]=[C:20]([F:22])[CH:19]=[CH:18][C:17]=4[CH3:23])[CH2:14][C:13](=[O:24])[N:12]([CH2:25][C:26]([OH:28])=[O:27])[CH:11]3[C:33]3[CH:38]=[CH:37][CH:36]=[C:35]([Cl:39])[CH:34]=3)[C:5]2=[CH:4][CH:3]=1

参加物

5

反応物 3

HCID 6422Trifluoroacetic acidHCID 81531DiisopropylethylamineHCID 77581377racemic (2'S,3S,4'R)-6-chloro-2'-(3-chlorophenyl)-4'-(5-fluoro-2-methyl-phenyl)-2,3-dihydro-1'-[(tert-butoxycarbonyl)methyl]-2,6'-dioxo spiro[indole-3,3'-piperidine] 1-methoxyethyl trimethylsilane

生成物 1

HCID 76568188racemic (2'S,3S,4'R)-6-chloro-2'-(3-chlorophenyl)-4'-(5-fluoro-2-methyl-phenyl)-1'-hydroxycarbonylmethyl-spiro[3H-indole-3,3'-piperidine]-2,6'(1H)-dione収率 70.1%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

To a solution of racemic (2′S,3S,4′R)-6-chloro-2′-(3-chlorophenyl)-4′-(5-fluoro-2-methyl-phenyl)-2,3-dihydro-1′-[(tert-butoxycarbonyl)methyl]-2,6′-dioxospiro[indole-3,3′-piperidine]-1-methoxyethyl trimethylsilane (0.85 g, 1.19 mmol) prepared in example 146d in dichloromethane (10 mL) was added trifluoroacetic acid (20 mL). The reaction mixture was stirred at room temperature for 18 h. The reaction mixture was concentrated. The residue was redissolved in methanol (10 mL). To the resulting solution was added N,N′-diisopropylethylamine (1.57 mL, 8.70 mmol) and the crude was refluxed for 1 h. The reaction mixture was concentrated and the residue was partitioned between ethyl acetate and HCl aqueous solution (1N). The organic layer was separated, dried over MgSO4 and concentrated. The residue was triturated with ethyl acetate and hexane to give racemic (2′S,3S,4′R)-6-chloro-2′-(3-chlorophenyl)-4′-(5-fluoro-2-methyl-phenyl)-1′-hydroxycarbonylmethyl-spiro[3H-indole-3,3′-piperidine]-2,6′(1H)-dione as a yellow solid (Yield 440 mg, 70%).

後処理

  1. concentrationThe reaction mixture was concentrated
  2. dissolutionThe residue was redissolved in methanol (10 mL)
  3. temperaturethe crude was refluxed for 1 h
  4. concentrationThe reaction mixture was concentrated
  5. customthe residue was partitioned between ethyl acetate and HCl aqueous solution (1N)
  6. customThe organic layer was separated
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated
  9. customThe residue was triturated with ethyl acetate and hexane

出典と根拠

ORDレコード
ord-b12c56497ee24f4eb3a2512decd2d70e
出典データセット
uspto-grants-2009_02
特許番号
US07495007B2

反応ノート

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