Water → Ethyl 2-methyl-3-{7-[(methylsulfanyl)methyl]-1H-indol-3-yl}-3-[4-(trifluoromethyl)phenyl]propanoate

HRID 561391Notes

Reaction equation

HRID 561391 reaction equation
[CH2:1]([O:3][C:4](=[O:37])[CH:5]([CH3:36])[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(OC(C)(C)C)=O)[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].FC(F)(F)C(O)=O.O>ClCCl>[CH3:36][CH: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)[NH:19][CH:18]=1)[C:7]1[CH:12]=[CH:11][C:10]([C:13]([F:15])([F:14])[F:16])=[CH:9][CH:8]=1)[C:4]([O:3][CH2:1][CH3:2])=[O:37]

Participants

5

Reactant 3

HCID 962WaterHCID 6422Trifluoroacetic acidHCID 58392421tert-Butyl 3-{3-ethoxy-2-methyl-3-oxo-1-[4-(trifluoromethyl)phenyl]propyl}-7-[(methylsulfanyl)methyl]-1H-indole-1-carboxylate

Product 1

HCID 58392300Ethyl 2-methyl-3-{7-[(methylsulfanyl)methyl]-1H-indol-3-yl}-3-[4-(trifluoromethyl)phenyl]propanoate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

2.52 g (4.71 mmol) of the compound from Example 27A were dissolved in 70 ml of dichloromethane, and 14.5 ml (188.56 mmol) of trifluoroacetic acid were added. After stirring at RT for 3 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 washed with saturated aqueous sodium bicarbonate solution and dried over sodium sulfate, the solid was filtered off and the solvents were removed in vacuo. Purification of the crude product by flash chromatography on silica gel (mobile phase: dichloromethane/methanol 95/5) and preparative HPLC (mobile phase: acetonitrile-water gradient) resulted in 1.01 g (48% of theory) of the title compound as mixture of diasteromers.

Workup

  1. customthe phases were separated
  2. extractionthe aqueous phase was extracted twice with ethyl acetate
  3. washThe combined organic phases were washed with saturated aqueous sodium bicarbonate solution
  4. dry with materialdried over sodium sulfate
  5. filtrationthe solid was filtered off
  6. customthe solvents were removed in vacuo
  7. customPurification of the crude product by flash chromatography on silica gel (mobile phase: dichloromethane/methanol 95/5) and preparative HPLC (mobile phase: acetonitrile-water gradient)

Sources & evidence

ORD record
ord-924be0196b524d88bcdb246a4fed5b28
Source dataset
uspto-grants-2011_11
Patent number
US08063234B2

Reaction notes

Loading…