Nitrogen → {4-[2-(3,4,5-Trimethoxy-phenyl)-acetyl]-piperazin-1-yl}-acetic acid ethyl ester

HRID 1944258

Reaction equation

HRID 1944258 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][C:35]([OH:37])=O)[CH:27]=[C:28]([O:32][CH3:33])[C:29]=1[O:30][CH3:31].[CH2:38]([O:40][C:41]([CH2:43][N:44]1[CH2:49][CH2:48][NH:47][CH2:46][CH2:45]1)=[O:42])[CH3:39]>C(Cl)Cl.CN(C1C=CN=CC=1)C>[CH2:38]([O:40][C:41](=[O:42])[CH2:43][N:44]1[CH2:49][CH2:48][N:47]([C:35](=[O:37])[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)[CH2:46][CH2:45]1)[CH3:39]

Participants

8

Reactant 5

HCID 947NitrogenHCID 8471TriethylamineHCID 703723,4,5-Trimethoxyphenylacetic acidHCID 207112Ethyl piperazine-1-acetateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride

Product 1

HCID 59785709{4-[2-(3,4,5-Trimethoxy-phenyl)-acetyl]-piperazin-1-yl}-acetic acid ethyl esterYield 40%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

(The following reaction is done in an anhydrous N2 atmosphere.) Suspend EDC HCl (188 mg, 0.98 mmol) and Et3N (137 μL, 0.98 mmol) in anhydrous DCM (1.0 mL) and stir the resulting solution for 5 min at rt. Add 2-(3,4,5-Trimethoxy-phenyl)-acetic acid (163 mg, 0.72 mmol) and DMAP (8 mg, 0.07 mmol) and stir the resulting solution for 10 min. Add 1-(Ethoxycarbonylmethyl)piperazine (43) (112 mg, 0.65 mmol) and stir the reaction solution overnight at rt. Quench reaction solution with sat. aqu. NH4Cl and water, separate layers and extract aqu. layer with DCM (3 times). Wash the combined organic layer with water and brine and dry with Na2SO4. Purify the crude product by preparative radial chromatography (silica gel, EtOAc/MeOH 10+1) to obtain {4-[2-(3,4,5-Trimethoxy-phenyl)-acetyl]-piperazin-1-yl}-acetic acid ethyl ester (44) (99 mg, 40%) as a colorless oil. 1H NMR (400 MHz, CDCl3): 1.25 (t, 3H, J=7.1 Hz); 2.48 (br.m, 2H); 2.58 (br.m, 2H); 3.21 (br.s, 2H); 3.53 (br.m, 2H); 3.65 (s, 2H); 3.71 (br.m, 2H); 3.81 (s, 3H); 3.82 (s, 6H); 4.16 (q, 2H, J=7.1 Hz); 6.42 (s, 2H).

Workup

  1. custom(The following reaction
  2. customQuench
  3. customreaction solution with sat. aqu
  4. customNH4Cl and water, separate layers
  5. extractionextract aqu
  6. washWash the combined organic layer with water and brine
  7. dry with materialdry with Na2SO4
  8. customPurify the crude product by preparative radial chromatography (silica gel, EtOAc/MeOH 10+1)

Sources & evidence

ORD record
ord-94f14d83acd84f01b6d09c49460a1872
Source dataset
uspto-grants-2013_03
Patent number
US08394835B2

Linked notes

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