Diisopropylethylamine → (E)-N-(4-(2-(dimethylamino)ethoxy)phenyl)-2-(4-(methoxymethoxy)phenyl)-3-phenylpent-2-enamide

HRID 884052Notes

Reaction equation

HRID 884052 reaction equation
[CH3:1][O:2][CH2:3][O:4][C:5]1[CH:10]=[CH:9][C:8](/[C:11](=[C:15](\[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)/[CH2:16][CH3:17])/[C:12]([OH:14])=O)=[CH:7][CH:6]=1.Cl.Cl.[CH3:26][N:27]([CH3:38])[CH2:28][CH2:29][O:30][C:31]1[CH:36]=[CH:35][C:34]([NH2:37])=[CH:33][CH:32]=1.C(N(CC)C(C)C)(C)C>CN(C)C1C=CN=CC=1.C(Cl)Cl>[CH3:26][N:27]([CH3:38])[CH2:28][CH2:29][O:30][C:31]1[CH:36]=[CH:35][C:34]([NH:37][C:12](=[O:14])/[C:11](/[C:8]2[CH:9]=[CH:10][C:5]([O:4][CH2:3][O:2][CH3:1])=[CH:6][CH:7]=2)=[C:15](/[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)\[CH2:16][CH3:17])=[CH:33][CH:32]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 574247414-[2-(Dimethylamino)ethoxy]aniline dihydrochlorideHCID 57693045(E)-2-(4-(methoxymethoxy)phenyl)-3-phenylpent-2-enoic acid

Product 1

HCID 57693048(E)-N-(4-(2-(dimethylamino)ethoxy)phenyl)-2-(4-(methoxymethoxy)phenyl)-3-phenylpent-2-enamideYield 65%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a mixture of 3 (2.90 g, 9.28 mmol), 4-(2-(dimethylamino)ethoxy)benzenamine dihydrochloride (2.58 g, 10.2 mmol), 4-Dimethylaminopyridine (56.7 mg, 0.464 mmol) in CH2Cl2 (100 ml) was added O-Benzotriazoyl-N,N,N′,N′-tetramethyluronium Hexafluorophosphate (3.87 g, 10.2 mmol) under ice cooling, and the mixture was stirred at 0° C. for 10 min. Then N,N-Diisopropylethylamine (4.19 g, 32.4 mmol) was added under ice cooling. The mixture was stirred at 0° C. for 5 min, and at room temperature for 15 h. The reaction was quenched with saturated aqueous NaHCO3 under ice cooling, and the whole was extracted with CHCl3, the organic layer was washed with brine, dried over Na2SO4, and then concentrated. Purification by Biotage (eluent: CH2Cl2 to CH2Cl2/MeOH, 6:1) gave the colorless solid. The solid was triturated with Et2O-hexane to give 4 (65%).

Workup

  1. stirringThe mixture was stirred at 0° C. for 5 min
  2. waitat room temperature for 15 h
  3. customThe reaction was quenched with saturated aqueous NaHCO3 under ice cooling
  4. extractionthe whole was extracted with CHCl3
  5. washthe organic layer was washed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated
  8. customPurification by Biotage (eluent: CH2Cl2 to CH2Cl2/MeOH, 6:1)
  9. customgave the colorless solid
  10. customThe solid was triturated with Et2O-hexane

Sources & evidence

ORD record
ord-bd615208740641bb90c3637a809a53e5
Source dataset
uspto-grants-2012_08
Patent number
US08236987B2

Reaction notes

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