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

HRID 899883Notes

Reaction equation

HRID 899883 reaction equation
[CH2:1]([N:5]([CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[C:20]([O:24][CH3:25])[C:19]=1[O:26][CH3:27])[C:6](=[O:16])[CH2:7][CH2:8][C:9]1[CH:14]=[CH:13][C:12]([OH:15])=[CH:11][CH:10]=1)[CH2:2][CH2:3][CH3:4].Br[CH2:29][C:30]1[CH:39]=[CH:38][CH:37]=[CH:36][C:31]=1[C:32]([O:34][CH3:35])=[O:33].C(=O)([O-])[O-].[K+].[K+].C(O)C(N)(CO)CO>C(#N)C>[CH2:1]([N:5]([CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[C:20]([O:24][CH3:25])[C:19]=1[O:26][CH3:27])[C:6](=[O:16])[CH2:7][CH2:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][CH2:29][C:30]2[CH:39]=[CH:38][CH:37]=[CH:36][C:31]=2[C:32]([O:34][CH3:35])=[O:33])=[CH:11][CH:10]=1)[CH2:2][CH2:3][CH3:4]

Participants

6

Reactant 4

HCID 6503Tris(hydroxymethyl)aminomethaneHCID 11430Potassium CarbonateHCID 2734813Methyl 2-(bromomethyl)benzoateHCID 69120686N-butyl-N-(2,3-dimethoxybenzyl)-3-(4-hydroxyphenyl)propanamide

Product 1

HCID 69120444Methyl 2-[(4-{3-[butyl(2,3-dimethoxybenzyl)amino]-3-oxopropyl}phenoxy)methyl]benzoateYield 22.2%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
60 °C

Procedure

N-butyl-N-(2,3-dimethoxybenzyl)-3-(4-hydroxyphenyl)propanamide (50 mg, 0.13 mmol) and methyl 2-(bromomethyl)benzoate (0.034 g, 0.15 mmol) was dissolved in acetonitrile (10 ml) and potassium carbonate (37 mg, 0.27 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 and solvent was removed by evaporation. EtOAc (10 ml) was added and the organic phase was washed with three portions of water. After drying the crude (MgSO4), the solvent had been removed by evaporation. The residue 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 15 mg of methyl 2-[(4-{3-[butyl(2,3-dimethoxybenzyl)amino]-3-oxopropyl}phenoxy)methyl]benzoate (21.4%).

Workup

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

Sources & evidence

ORD record
ord-fd0ac2e4bd91408a8a97f92533e2f2e9
Source dataset
uspto-grants-2008_04
Patent number
US07355069B2

Reaction notes

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