Nitrogen → {4-[3-(3,4,5-Trimethoxy-phenyl)-propionyl]-piperazin-1-yl}-acetic acid ethyl ester

HRID 2075930

Reaction equation

HRID 2075930 reaction equation
N#N.CCN=C=NCCCN(C)C.Cl.CCN(CC)CC.[CH3:22][O:23][C:24]1[CH:25]=[C:26]([CH2:34][CH2:35][C:36]([OH:38])=O)[CH:27]=[C:28]([O:32][CH3:33])[C:29]=1[O:30][CH3:31].[CH2:39]([O:41][C:42]([CH2:44][N:45]1[CH2:50][CH2:49][NH:48][CH2:47][CH2:46]1)=[O:43])[CH3:40]>C(Cl)Cl.CN(C1C=CN=CC=1)C>[CH2:39]([O:41][C:42](=[O:43])[CH2:44][N:45]1[CH2:50][CH2:49][N:48]([C:36](=[O:38])[CH2:35][CH2:34][C:26]2[CH:27]=[C:28]([O:32][CH3:33])[C:29]([O:30][CH3:31])=[C:24]([O:23][CH3:22])[CH:25]=2)[CH2:47][CH2:46]1)[CH3:40]

Participants

8

Reactant 5

HCID 947NitrogenHCID 8471TriethylamineHCID 648603,4,5-Trimethoxyhydrocinnamic acidHCID 207112Ethyl piperazine-1-acetateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride

Product 1

HCID 59785706{4-[3-(3,4,5-Trimethoxy-phenyl)-propionyl]-piperazin-1-yl}-acetic acid ethyl esterYield 83.1%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

(The following reaction is done in an anhydrous N2 atmosphere.) Suspend EDC.HCl (376 mg, 1.96 mmol) and Et3N (275 μL, 1.96 mmol) in anhydrous DCM (2.0 mL) and stir the resulting solution for 5 min at rt. Add 3-(3,4,5-Trimethoxy-phenyl)-propionic acid (346 mg, 1.44 mmol) and DMAP (17 mg, 0.14 mmol) and stir the resulting solution for 15 min. Add 1-(Ethoxycarbonylmethyl)piperazine (43) (224 mg, 1.30 mmol) and stir the reaction solution overnight at rt. Quench reaction solution with water, separate layers and extract aqu. layer with EtOAc (3 times). Filtrate the combined organic layer through a short pad of silica gel and remove solvent. Purify the crude product by preparative radial chromatography (silica gel, EtOAc/MeOH 9+1) to obtain {4-[3-(3,4,5-Trimethoxy-phenyl)-propionyl]-piperazin-1-yl}-acetic acid ethyl ester (45) (426 mg, 83%) as a colorless oil. 1H NMR (400 MHz, CDCl3): 1.26 (t, 3H, J=7.1 Hz); 2.45-2.70 (br.m, 6H); 2.89 (t, 2H, J=7.7 Hz); 3.26 (br.s, 2H); 3.43-3.56 (br.m, 2H); 3.61-3.76 (br.m, 2H); 3.80 (s, 3H); 3.83 (s, 6H); 4.18 (q, 2H, J=7.1 Hz); 6.41 (s, 2H).

Workup

  1. custom(The following reaction
  2. customQuench
  3. customreaction solution with water
  4. customseparate layers
  5. extractionextract aqu
  6. customFiltrate the combined organic layer through a short pad of silica gel and remove solvent
  7. customPurify the crude product by preparative radial chromatography (silica gel, EtOAc/MeOH 9+1)

Sources & evidence

ORD record
ord-d68bd0aff6ca40d294b647113c76ecc7
Source dataset
uspto-grants-2011_04
Patent number
US07923473B2

Linked notes

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