3-(4-Hydroxyphenyl)propionic acid → N-(3-ethoxypropyl)-3-(4-hydroxyphenyl)-N-(4-isopropylbenzyl)propanamide

HRID 899889

Reaction equation

HRID 899889 reaction equation
[CH2:1]([O:3][CH2:4][CH2:5][CH2:6][NH:7][CH2:8][C:9]1[CH:14]=[CH:13][C:12]([CH:15]([CH3:17])[CH3:16])=[CH:11][CH:10]=1)[CH3:2].[OH:18][C:19]1[CH:24]=[CH:23][C:22]([CH2:25][CH2:26][C:27](O)=[O:28])=[CH:21][CH:20]=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>CN(C=O)C.CCOC(C)=O>[CH2:1]([O:3][CH2:4][CH2:5][CH2:6][N:7]([CH2:8][C:9]1[CH:14]=[CH:13][C:12]([CH:15]([CH3:16])[CH3:17])=[CH:11][CH:10]=1)[C:27](=[O:28])[CH2:26][CH2:25][C:22]1[CH:23]=[CH:24][C:19]([OH:18])=[CH:20][CH:21]=1)[CH3:2]

Participants

7

Reactant 4

HCID 103943-(4-Hydroxyphenyl)propionic acidHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 4723366N-(3-ethoxypropyl)-N-(4-isopropylbenzyl)amine

Product 1

HCID 69120692N-(3-ethoxypropyl)-3-(4-hydroxyphenyl)-N-(4-isopropylbenzyl)propanamideYield 108.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

N-(3-ethoxypropyl)-N-(4-isopropylbenzyl)amine (0.62 g, 2.65 mmol) was dissolved in DMF (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 1.0 gram of N-(3-ethoxypropyl)-3-(4-hydroxyphenyl)-N-(4-isopropylbenzyl)propanamide (yield 75.8%).

Workup

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

Sources & evidence

ORD record
ord-8e1182eacfdb44619f23428420d8ef82
Source dataset
uspto-grants-2008_04
Patent number
US07355069B2

Linked notes

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