Ethyl Acetate → Methyl 2-[(4-{2-[ethyl(2-fluorobenzyl)amino]-2-oxoethoxy}phenoxy)methyl]benzoate

HRID 2112053Notes

Reaction equation

HRID 2112053 reaction equation
[CH2:1]([N:3]([CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[F:22])[C:4](=[O:14])[CH2:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([OH:13])=[CH:9][CH:8]=1)[CH3:2].Br[CH2:24][C:25]1[CH:34]=[CH:33][CH:32]=[CH:31][C:26]=1[C:27]([O:29][CH3:30])=[O:28].C(=O)([O-])[O-].[K+].[K+].CCOC(C)=O>C(#N)C>[CH2:1]([N:3]([CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[F:22])[C:4](=[O:14])[CH2:5][O:6][C:7]1[CH:8]=[CH:9][C:10]([O:13][CH2:24][C:25]2[CH:34]=[CH:33][CH:32]=[CH:31][C:26]=2[C:27]([O:29][CH3:30])=[O:28])=[CH:11][CH:12]=1)[CH3:2]

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 2734813Methyl 2-(bromomethyl)benzoateHCID 68868696N-ethyl-N-(2-fluorobenzyl)-2-(4-hydroxyphenoxy)acetamide

Product 1

HCID 68869777Methyl 2-[(4-{2-[ethyl(2-fluorobenzyl)amino]-2-oxoethoxy}phenoxy)methyl]benzoateYield 91.9%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
60 °C

Procedure

N-Ethyl-N-(2-fluorobenzyl)-2-(4-hydroxyphenoxy)acetamide (0.177 g, 0.586 mmol) was dissolved in acetonitrile (10 ml), methyl 2-(bromomethyl)benzoate (0.147 g, 0.642 mmol) and dipotassium carbonate (0.161 g, 1.167 mmol) were added. The solution was stirred for 2 hours at 60° C. EtOAc (20 ml) was added and the organic phase was washed with two portions of brine (2×20 ml, aq). The organic layer was dried (MgSO4) and the solvent was removed by evaporation. The crude was purified by preparative HPLC (started with isocratic acetonitrile/buffer 60/40 and then the acetonitrile concentration was increased to 100%, the buffer was a mixture of acetonitrile/water 10/90 and ammonium acetate (0.1 M, column KR-100-7-C8, 50 mm×250 mm, flow 40 ml/min). The product containing fractions were pooled and the acetonitrile was removed by evaporation. EtOAc (10 ml) was added and the organic phase was washed with two portions of brine and dried (MgSO4) and the solvent was removed by evaporation to give 0.242 g of methyl 2-[(4-{2-[ethyl(2-fluorobenzyl)amino]-2-oxoethoxy}phenoxy)methyl]benzoate (yield 91.9%).

Workup

  1. washthe organic phase was washed with two portions of brine (2×20 ml, aq)
  2. dry with materialThe organic layer was dried (MgSO4)
  3. customthe solvent was removed by evaporation
  4. customThe crude was purified by preparative HPLC (
  5. concentrationthe acetonitrile concentration
  6. temperaturewas increased to 100%
  7. additiona mixture of acetonitrile/water 10/90 and ammonium acetate (0.1 M, column KR-100-7-C8, 50 mm×250 mm, flow 40 ml/min)
  8. additionThe product containing fractions
  9. customthe acetonitrile was removed by evaporation
  10. additionEtOAc (10 ml) was added
  11. washthe organic phase was washed with two portions of brine
  12. dry with materialdried (MgSO4)
  13. customthe solvent was removed by evaporation

Sources & evidence

ORD record
ord-fc4ff127a3f9445aad229ea9667aaa27
Source dataset
uspto-grants-2009_04
Patent number
US07521461B2

Reaction notes

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