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

HRID 561390노트

반응식

HRID 561390 반응식
[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]

참가 물질

7

반응물 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

생성물 1

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

시약·촉매·용매 2

HCID 8028Tetrahydrofuran용매HCID 21263495Tetrahydrofuran heptane용매

반응 조건

온도
-78 °C

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-804c576b48624669a6655be641a57b95
출처 데이터셋
uspto-grants-2011_11
특허 번호
US08063234B2

반응 노트

불러오는 중…