Tris(hydroxymethyl)aminomethane → HCID 69120410, compound

HRID 899886Notes

Reaction equation

HRID 899886 reaction equation
[CH3:1][O:2][C:3]1[C:28]([O:29][CH3:30])=[CH:27][CH:26]=[CH:25][C:4]=1[CH2:5][N:6]([CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH3:24])[C:7](=[O:17])[CH2:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([OH:16])=[CH:12][CH:11]=1.Br[CH2:32][C:33]1[CH:42]=[CH:41][CH:40]=[CH:39][C:34]=1[C:35]([O:37][CH3:38])=[O:36].C(=O)([O-])[O-].[K+].[K+].C(O)C(N)(CO)CO>C(#N)C>[CH3:1][O:2][C:3]1[C:28]([O:29][CH3:30])=[CH:27][CH:26]=[CH:25][C:4]=1[CH2:5][N:6]([CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH3:24])[C:7](=[O:17])[CH2:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([O:16][CH2:32][C:33]2[CH:42]=[CH:41][CH:40]=[CH:39][C:34]=2[C:35]([O:37][CH3:38])=[O:36])=[CH:12][CH:11]=1

Participants

6

Reactant 4

HCID 6503Tris(hydroxymethyl)aminomethaneHCID 11430Potassium CarbonateHCID 2734813Methyl 2-(bromomethyl)benzoateHCID 69120230HCID 69120230, compound

Product 1

HCID 69120410HCID 69120410, compoundYield 14.8%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
60 °C

Procedure

N-(2,3-dimethoxybenzyl)-N-heptyl-3-(4-hydroxyphenyl)propanamide 0.196 g, 0.47 mmol) and methyl 2-(bromomethyl)benzoate (0.12 g, 0.52 mmol) was dissolved in acetonitrile (10 ml) and potassiumcarbonate (131 mg, 0.95 mmol) was added. The mixture was stirred at 60° C. for three hours. Polymersupproted trisamine (0.3 eqv) was added and stirred over night. The polymer was filtered of, solvent was removed by evaporation, addition of EtOAc (10 ml) and the organic phase was washed with three potions of water. After drying the crude (MgSO4) and the solvent had been 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 was pooled and the acetonitrile was removed by evaporation. EtOAc (10 ml) was added and the organic phase was washed with two potions of brine and dried (MgSO4). Removing the solvent by evaporation gave 39 mg of methyl 2-[(4-{3-[(2,3-dimethoxybenzyl)(heptyl)amino]-3-oxopropyl}phenoxy)methyl]benzoate (yield 14.6%).

Workup

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

Sources & evidence

ORD record
ord-c822b3b413e74acb95c6084eb3ecc430
Source dataset
uspto-grants-2008_04
Patent number
US07355069B2

Reaction notes

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