Tris(hydroxymethyl)aminomethane → Methyl 2-{[4-(3-{[2-(2-ethoxyphenyl)ethyl]amino}-3-oxopropyl)phenoxy]methyl}benzoate

HRID 2112030Notes

Reaction equation

HRID 2112030 reaction equation
[CH2:1]([O:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[CH2:10][CH2:11][NH:12][C:13](=[O:23])[CH2:14][CH2:15][C:16]1[CH:21]=[CH:20][C:19]([OH:22])=[CH:18][CH:17]=1)[CH3:2].Br[CH2:25][C:26]1[CH:35]=[CH:34][CH:33]=[CH:32][C:27]=1[C:28]([O:30][CH3:31])=[O:29].C(=O)([O-])[O-].[K+].[K+].C(O)C(N)(CO)CO>C(#N)C>[CH2:1]([O:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[CH2:10][CH2:11][NH:12][C:13](=[O:23])[CH2:14][CH2:15][C:16]1[CH:17]=[CH:18][C:19]([O:22][CH2:25][C:26]2[CH:35]=[CH:34][CH:33]=[CH:32][C:27]=2[C:28]([O:30][CH3:31])=[O:29])=[CH:20][CH:21]=1)[CH3:2]

Participants

6

Reactant 4

HCID 6503Tris(hydroxymethyl)aminomethaneHCID 11430Potassium CarbonateHCID 2734813Methyl 2-(bromomethyl)benzoateHCID 68873053N-[2-(2-ethoxyphenyl)ethyl]-3-(4-hydroxyphenyl)propanamide

Product 1

HCID 68870250Methyl 2-{[4-(3-{[2-(2-ethoxyphenyl)ethyl]amino}-3-oxopropyl)phenoxy]methyl}benzoateYield 50.4%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
60 °C

Procedure

N-[2-(2-ethoxyphenyl)ethyl]-3-(4-hydroxyphenyl)propanamide (0.35 g, 1.12 mmol) and methyl 2-(bromomethyl)benzoate (0.28 g, 1.23 mmol) was dissolved in acetonitrile (5 ml) and potassium carbonate (324 mg, 2.34 mmol) was added. The mixture was stirred at 60° C. for three hours. Polymer supported trisamine (0.3 eqv) was added and stirred overnight. The polymer was filtered off, solvent was removed by evaporation, addition of EtOAc (10 ml) and the organic phase was washed with three portions of water. After drying the crude (MgSO4) and the solvent was removed by evaporation, the crude was purified by preparative HPLC (started with 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). Removing the solvent by evaporation gave 26 mg of methyl 2-{[4-(3-{[2-(2-ethoxyphenyl)ethyl]amino}-3-oxopropyl)phenoxy]methyl}benzoate (yield 50.4%).

Workup

  1. additionwas added
  2. stirringstirred overnight
  3. filtrationThe polymer was filtered off
  4. customsolvent was removed by evaporation, addition of EtOAc (10 ml)
  5. washthe organic phase was washed with three portions of water
  6. dry with materialAfter drying the crude (MgSO4)
  7. customthe solvent was removed by evaporation
  8. customthe crude was purified by preparative HPLC (
  9. concentrationthe acetonitrile concentration
  10. temperaturewas increased to 100%
  11. 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))
  12. additionThe product containing fractions
  13. customthe acetonitrile was removed by evaporation
  14. additionEtOAc (10 ml) was added
  15. washthe organic phase was washed with two portions of brine
  16. dry with materialdried (MgSO4)
  17. customRemoving the solvent
  18. customby evaporation

Sources & evidence

ORD record
ord-0667d547275044a2958d78075527a2fe
Source dataset
uspto-grants-2009_04
Patent number
US07521461B2

Reaction notes

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