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

HRID 561390Notes

Reaction equation

HRID 561390 reaction equation
[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]

Participants

7

Reactant 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

Product 1

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

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 21263495Tetrahydrofuran heptaneSolvent

Conditions

Temperature
-78 °C

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-804c576b48624669a6655be641a57b95
Source dataset
uspto-grants-2011_11
Patent number
US08063234B2

Reaction notes

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