Tris(hydroxymethyl)aminomethane → HCID 68872140, compound

HRID 2112033Notes

Reaction equation

HRID 2112033 reaction equation
[CH2:1]([N:3]([CH2:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=1)[C:4](=[O:14])[CH2:5][CH2:6][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+].C(O)C(N)(CO)CO>C(#N)C>[CH2:1]([N:3]([CH2:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=1)[C:4](=[O:14])[CH2:5][CH2:6][C:7]1[CH:12]=[CH:11][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:9][CH:8]=1)[CH3:2]

Participants

6

Reactant 4

HCID 6503Tris(hydroxymethyl)aminomethaneHCID 11430Potassium CarbonateHCID 2734813Methyl 2-(bromomethyl)benzoateHCID 68871483HCID 68871483, compound

Product 1

HCID 68872140HCID 68872140, compoundYield 25.8%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
60 °C

Procedure

N-Ethyl-3-(4-hydroxyphenyl)-N-(2-pyridin-2-ylethyl)propanamide (0.35 g, 1.17 mmol) and methyl 2-(bromomethyl)benzoate (0.30 g, 1.29 mmol) were 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, EtOAc (10 ml) was added and the organic phase was washed with three portions of water. After drying the organic layer (MgSO4), 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 135 mg of methyl 2-[(4-{3-[ethyl(2-pyridin-2-ylethyl)amino]-3-oxopropyl}phenoxy)methyl]benzoate (yield 25.8%).

Workup

  1. additionwas added
  2. stirringstirred overnight
  3. filtrationThe polymer was filtered off
  4. customsolvent was removed by evaporation, EtOAc (10 ml)
  5. additionwas added
  6. washthe organic phase was washed with three portions of water
  7. dry with materialAfter drying the organic layer (MgSO4)
  8. customthe solvent was removed by evaporation
  9. customThe crude 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 EtOAc (10 ml)
  15. additionwas 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-a0d46389fc6041418e6f1f0abebda17d
Source dataset
uspto-grants-2009_04
Patent number
US07521461B2

Reaction notes

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