Water → tert-Butyl 3-{3-ethoxy-2-methyl-3-oxo-1-[4-(trifluoromethyl)phenyl]propyl}-7-[(methylsulfanyl)methyl]-1H-indole-1-carboxylate

HRID 561390ノート

反応式

HRID 561390 の反応式
[CH2:1]([O:3][C:4](=[O:36])[CH2:5][CH:6]([C:17]1[C:25]2[C:20](=[C:21]([CH2:26][S:27][CH3:28])[CH:22]=[CH:23][CH:24]=2)[N:19]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH:18]=1)[C:7]1[CH:12]=[CH:11][C:10]([C:13]([F:16])([F:15])[F:14])=[CH:9][CH:8]=1)[CH3:2].[CH:37]([N-]C(C)C)(C)C.[Li+].IC.O>O1CCCC1.O1CCCC1.CCCCCCC>[CH2:1]([O:3][C:4](=[O:36])[CH:5]([CH3:37])[CH:6]([C:17]1[C:25]2[C:20](=[C:21]([CH2:26][S:27][CH3:28])[CH:22]=[CH:23][CH:24]=2)[N:19]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH:18]=1)[C:7]1[CH:12]=[CH:11][C:10]([C:13]([F:15])([F:16])[F:14])=[CH:9][CH:8]=1)[CH3:2]

参加物

7

反応物 4

HCID 962WaterHCID 6328Methyl iodideHCID 2724682Lithium diisopropylamideHCID 58392145tert-Butyl 3-{3-ethoxy-3-oxo-1-[4-(trifluoromethyl)phenyl]propyl}-7-[(methylsulfanyl)methyl]-1H-indole-1-carboxylate

生成物 1

HCID 58392421tert-Butyl 3-{3-ethoxy-2-methyl-3-oxo-1-[4-(trifluoromethyl)phenyl]propyl}-7-[(methylsulfanyl)methyl]-1H-indole-1-carboxylate

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒HCID 21263495Tetrahydrofuran heptane溶媒

反応条件

温度
-78 °C

実験手順

1.60 g (3.07 mmol) of the compound from Example 26A were dissolved in tetrahydrofuran at −78° C., and 3.2 ml (6.44 mmol) of a 2N solution of lithium diisopropylamide in tetrahydrofuran/n-heptane were slowly added dropwise. After 5 min, 0.40 ml (6.44 mmol) of iodomethane was added, and the mixture was stirred at −78° C. for 2 h and then warmed to RT over the course of a further 2 h. The reaction solution was mixed with water, the phases were separated, and the aqueous phase was extracted twice with ethyl acetate. The combined organic phases were dried over sodium sulfate, the solid was filtered off, and the solvents were removed in vacuo. The crude product was purified by preparative HPLC (mobile phase: acetonitrile-water gradient) to result in 1.20 g (73% of theory) of the title compound as mixture of diasteromers.

後処理

  1. temperaturewarmed to RT over the course of a further 2 h
  2. customthe phases were separated
  3. extractionthe aqueous phase was extracted twice with ethyl acetate
  4. dry with materialThe combined organic phases were dried over sodium sulfate
  5. filtrationthe solid was filtered off
  6. customthe solvents were removed in vacuo
  7. customThe crude product was purified by preparative HPLC (mobile phase: acetonitrile-water gradient)

出典と根拠

ORDレコード
ord-804c576b48624669a6655be641a57b95
出典データセット
uspto-grants-2011_11
特許番号
US08063234B2

反応ノート

読み込み中…