Ethyl bromoacetate → Tert-butyl 3-(4-{[(2-ethoxy-2-oxoethyl)(2-furylmethyl)amino]methyl}phenyl)-2,2-dimethylpropionate

HRID 1266504Notes

Reaction equation

HRID 1266504 reaction equation
[O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[CH2:6][NH:7][CH2:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][C:16]([CH3:25])([CH3:24])[C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])=[CH:11][CH:10]=1.C(N(CC)CC)C.Br[CH2:34][C:35]([O:37][CH2:38][CH3:39])=[O:36]>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.C1COCC1>[CH2:38]([O:37][C:35](=[O:36])[CH2:34][N:7]([CH2:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][C:16]([CH3:25])([CH3:24])[C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])=[CH:11][CH:10]=1)[CH2:6][C:2]1[O:1][CH:5]=[CH:4][CH:3]=1)[CH3:39]

Participants

6

Reactant 3

HCID 7748Ethyl bromoacetateHCID 8471TriethylamineHCID 22708175Tert-butyl 3-(4-{[(2-furylmethyl)amino]methyl}phenyl)-2,2-dimethylpropionate

Product 1

HCID 22708222Tert-butyl 3-(4-{[(2-ethoxy-2-oxoethyl)(2-furylmethyl)amino]methyl}phenyl)-2,2-dimethylpropionateYield 94%

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 600 mg (1.75 mmol) of tert-butyl 3-(4-{[(2-furylmethyl)amino]-methyl}phenyl)-2,2-dimethylpropionate (Example I-5), 323 mg (0.87 mmol) of tetra-n-butylammonium iodide and 265 mg (2.62 mmol) of triethylamine in 10 ml of THF is treated with 438 mg (2.62 mmol) of ethyl bromoacetate and heated at reflux overnight. After cooling, the mixture is concentrated under reduced pressure, the residue is taken up in water and ethyl acetate, the aqueous phase is extracted 2× with ethyl acetate and the combined organic phases are washed with NaCl solution and dried over sodium sulphate. The solvent is removed under reduced pressure, and chromatographic purification on silica gel (cyclohexane→cyclohexane/ethyl acetate 10:1) then gives 702 mg (94%) of tert-butyl 3-(4-{[(2-ethoxy-2-oxoethyl)(2-furylmethyl)amino]methyl}phenyl)-2,2-di methylpropionate.

Workup

  1. temperatureheated
  2. temperatureat reflux overnight
  3. temperatureAfter cooling
  4. concentrationthe mixture is concentrated under reduced pressure
  5. extractionethyl acetate, the aqueous phase is extracted 2× with ethyl acetate
  6. washthe combined organic phases are washed with NaCl solution
  7. dry with materialdried over sodium sulphate
  8. customThe solvent is removed under reduced pressure, and chromatographic purification on silica gel (cyclohexane→cyclohexane/ethyl acetate 10:1)

Sources & evidence

ORD record
ord-9e8185ef4827456a951f8dbbdcc854e9
Source dataset
uspto-grants-2003_04
Patent number
US06548538B2

Reaction notes

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