3-(4-Hydroxyphenyl)propionic acid → HCID 69120230, compound

HRID 899885Notes

Reaction equation

HRID 899885 reaction equation
[CH3:1][O:2][C:3]1[C:17]([O:18][CH3:19])=[CH:16][CH:15]=[CH:14][C:4]=1[CH2:5][NH:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH3:13].[OH:20][C:21]1[CH:26]=[CH:25][C:24]([CH2:27][CH2:28][C:29]([OH:31])=O)=[CH:23][CH:22]=1.F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C>CCOC(C)=O>[CH3:1][O:2][C:3]1[C:17]([O:18][CH3:19])=[CH:16][CH:15]=[CH:14][C:4]=1[CH2:5][N:6]([CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH3:13])[C:29](=[O:31])[CH2:28][CH2:27][C:24]1[CH:23]=[CH:22][C:21]([OH:20])=[CH:26][CH:25]=1

Participants

6

Reactant 4

HCID 103943-(4-Hydroxyphenyl)propionic acidHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 4717570HCID 4717570, compound

Product 1

HCID 69120230HCID 69120230, compoundYield 98.3%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

N-(2,3-Dimethoxybenzyl)-N-heptylamine (0.70 g, 2.65 mmol) was dissolved in DM (10 ml), 3-(4-hydroxyphenyl)propanoic acid (0.4 g, 2.41 mmol), was added and the mixture was cooled to 0° C. N-[(1H-1,2,3-benzotriazol-1-yloxy)(dimethylamino)methylene]-N-methylmethanaminium tetrafluoroborate (0.85 g, 2.65 mmol) and diisopropylethylamine (0.65 g, 5.05 mmol) was added. The mixture was allowed to warm to room temperature and stirred overnight. EtOAc (15 ml) was added and the organic phase was washed with two portions of sodium hydrogencarbonate (aq, 10 ml). EtOAc was removed by evaporation and 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). The solvent was removed by evaporation and gave 0.98 gram N-(2,3-dimethoxybenzyl)-N-heptyl-3-(4-hydroxyphenyl)propanamide (yield 70%).

Workup

  1. additionwas added
  2. temperatureto warm to room temperature
  3. washthe organic phase was washed with two portions of sodium hydrogencarbonate (aq, 10 ml)
  4. customEtOAc was removed by evaporation
  5. customthe crude was purified by preparative HPLC (
  6. concentrationthe acetonitrile concentration
  7. temperaturewas increased to 100%
  8. 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)
  9. additionThe product containing fractions
  10. customthe acetonitrile was removed by evaporation
  11. additionEtOAc (10 ml) was added
  12. washthe organic phase was washed with two portions of brine
  13. dry with materialdried (MgSO4)
  14. customThe solvent was removed by evaporation

Sources & evidence

ORD record
ord-3fcd10837d1443c7b235b81e425b311a
Source dataset
uspto-grants-2008_04
Patent number
US07355069B2

Reaction notes

Loading…