Water → Cyclopropanecarboxylic acid{4-[6-(2-chloroethoxy)-3-cyano-1-ethyl-1h-indol-2-yl]-phenyl}-amide

HRID 506104Notes

Reaction equation

HRID 506104 reaction equation
[C:1]([C:3]1[C:11]2[C:6](=[CH:7][C:8]([OH:12])=[CH:9][CH:10]=2)[N:5]([CH2:13][CH3:14])[C:4]=1[C:15]1[CH:20]=[CH:19][C:18]([NH:21][C:22]([CH:24]2[CH2:26][CH2:25]2)=[O:23])=[CH:17][CH:16]=1)#[N:2].C([O-])([O-])=O.[K+].[K+].Br[CH2:34][CH2:35][Cl:36].O>CCC(C)=O.C(OCC)(=O)C>[Cl:36][CH2:35][CH2:34][O:12][C:8]1[CH:7]=[C:6]2[C:11]([C:3]([C:1]#[N:2])=[C:4]([C:15]3[CH:20]=[CH:19][C:18]([NH:21][C:22]([CH:24]4[CH2:26][CH2:25]4)=[O:23])=[CH:17][CH:16]=3)[N:5]2[CH2:13][CH3:14])=[CH:10][CH:9]=1

Participants

7

Reactant 4

HCID 962WaterHCID 78491-Bromo-2-ChloroethaneHCID 11430Potassium CarbonateHCID 59425200cyclopropanecarboxylic acid [4-(3-cyano-1-ethyl-6-hydroxy-1H-indol-2-yl)-phenyl]-amide

Product 1

HCID 59426127Cyclopropanecarboxylic acid{4-[6-(2-chloroethoxy)-3-cyano-1-ethyl-1h-indol-2-yl]-phenyl}-amideYield 81%

Reagents, catalysts & solvents 2

HCID 6569Methyl Ethyl KetoneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of cyclopropanecarboxylic acid [4-(3-cyano-1-ethyl-6-hydroxy-1H-indol-2-yl)-phenyl]-amide (4 g, 11.6 mmol) in 15 mL of MEK is added K2CO3 (8 g, 58 mmol) and 1-bromo-2-chloro-ethane (6.7 mL, 70 mmol). Then the mixture is heated at reflux overnight. After it is cooled to room temperature, water and ethyl acetate are added. The organic layer is separated, washed with brine (2×), dried over anhydrous Na2SO4, filtered and concentrated to yield 81% of the crude cyclopropanecarboxylic acid{4-[6-(2-chloroethoxy)-3-cyano-1-ethyl-1H-indol-2-yl]-phenyl}-amide.

Workup

  1. temperatureThen the mixture is heated
  2. temperatureat reflux overnight
  3. customThe organic layer is separated
  4. washwashed with brine (2×)
  5. dry with materialdried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-3d44bf32c45d41818a9b2a1202fe6f7e
Source dataset
uspto-grants-2010_08
Patent number
US07781478B2

Reaction notes

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