Ethyl bromoacetate → ethyl [5-[2-[N-tert-butoxycarbonyl-2-(2-ethoxyphenoxy)ethylamino]propyl]-7-cyanoindolin-1-yl]acetate

HRID 273861Notes

Reaction equation

HRID 273861 reaction equation
[C:1]([O:5][C:6]([N:8]([CH2:23][CH2:24][O:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=1[O:32][CH2:33][CH3:34])[CH:9]([CH3:22])[CH2:10][C:11]1[CH:12]=[C:13]2[C:17](=[C:18]([C:20]#[N:21])[CH:19]=1)[NH:16][CH2:15][CH2:14]2)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1CC2OCCOCCOC3C(OCCOCCOC2CC1)CCCC3.C(=O)([O-])[O-].[K+].[K+].Br[CH2:68][C:69]([O:71][CH2:72][CH3:73])=[O:70]>O1CCCC1.O>[C:1]([O:5][C:6]([N:8]([CH2:23][CH2:24][O:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=1[O:32][CH2:33][CH3:34])[CH:9]([CH3:22])[CH2:10][C:11]1[CH:12]=[C:13]2[C:17](=[C:18]([C:20]#[N:21])[CH:19]=1)[N:16]([CH2:68][C:69]([O:71][CH2:72][CH3:73])=[O:70])[CH2:15][CH2:14]2)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 7748Ethyl bromoacetateHCID 11430Potassium CarbonateHCID 85955Dicyclohexano-18-crown-6HCID 200943835-[2-[N-tert-butoxycarbonyl-2-(2-ethoxyphenoxy)ethylamino]propyl]indoline-7-carbonitrile

Product 1

HCID 54563971ethyl [5-[2-[N-tert-butoxycarbonyl-2-(2-ethoxyphenoxy)ethylamino]propyl]-7-cyanoindolin-1-yl]acetateYield 34.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 5-[2-[N-tert-butoxycarbonyl-2-(2-ethoxyphenoxy)ethylamino]propyl]indoline-7-carbonitrile (300 mg) and cis-dicyclohexano-18-crown-6 (24 mg) in dry tetrahydrofuran (4 ml) were added potassium carbonate (107 mg) and ethyl bromoacetate (129 mg), and the mixture was reacted in a sealed tube at 100° C. for 24 hours. To the reaction mixture was added water, and the mixture was extracted with ethyl acetate. The extract was washed with water, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by medium pressure liquid column chromatography on silica gel using a mixture of hexane and ethyl acetate (1/2) as eluent to give 124 mg of ethyl [5-[2-[N-tert-butoxycarbonyl-2-(2-ethoxyphenoxy)ethylamino]propyl]-7-cyanoindolin-1-yl]acetate as an oil.

Workup

  1. customthe mixture was reacted in a sealed tube at 100° C. for 24 hours
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe extract was washed with water
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customThe solvent was evaporated under reduced pressure
  6. customthe residue was purified by medium pressure liquid column chromatography on silica gel using
  7. additiona mixture of hexane and ethyl acetate (1/2) as eluent

Sources & evidence

ORD record
ord-63e47cdffe844f659c08becf42d38ae2
Source dataset
uspto-grants-1995_02
Patent number
US05387603

Reaction notes

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