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Malonic Acid → Ethyl (Z)-N-(3,4-dichlorobenzyl)-2-ethoxycarbonylindole-3-acrylic acid

HRID 2307930
Notes
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Reaction equation

HRID 2307930 reaction equation
[C:1](O)(=O)[CH2:2][C:3]([OH:5])=[O:4].C([C:10]1[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[N:12]([CH2:19][C:20]2[CH:25]=[CH:24][C:23]([Cl:26])=[C:22]([Cl:27])[CH:21]=2)[C:11]=1[C:28]([O:30][CH2:31][CH3:32])=[O:29])=O.N1C=CC=[CH:35][CH:34]=1>N1CCCCC1>[CH2:34]([C:17]1[CH:16]=[CH:15][CH:14]=[C:13]2[C:18]=1[C:10](/[CH:1]=[CH:2]\[C:3]([OH:5])=[O:4])=[C:11]([C:28]([O:30][CH2:31][CH3:32])=[O:29])[N:12]2[CH2:19][C:20]1[CH:25]=[CH:24][C:23]([Cl:26])=[C:22]([Cl:27])[CH:21]=1)[CH3:35]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

5

Reactant 3

HCID 867Malonic AcidHCID 1049PyridineHCID 22603427Ethyl 3-formyl-N-(3,4-dichlorobenzyl)indole-2-carboxylate

Product 1

HCID 86759582Ethyl (Z)-N-(3,4-dichlorobenzyl)-2-ethoxycarbonylindole-3-acrylic acidYield 19%

Reagents, catalysts & solvents 1

HCID 8082PiperidineCatalyst

Conditions

Temperature
100 °C

Procedure

Malonic acid (106 mg) and piperidine (1 drop) were added to a solution of ethyl 3-formyl-N-(3,4-dichlorobenzyl)indole-2-carboxylate (315 mg) in pyridine (5 ml) and the reaction stirred at 100° C. overnight. The reaction was concentrated in vacuo and the residue dissolved in ethyl acetate (30 ml), washed with HCl (2M, 30 ml) and water (30 ml), dried (MgSO4) and concentrated in vacuo to give the crude product which was triturated with a mixture of dichloromethane, ethyl acetate and hexane to give the product as a tan coloured solid (68 mg, 19%); NMR d (CD3SOCD3) 1.25 (t, 3H), 4.35 (q, 2H), 5.80 (s, 2H), 6.55 (d, 1H), 6.90 (m, 1H), 7.25-7.45 (m, 3H), 7.50 (m, 1H), 7.60 (m, 1H), 8.05 (m, 1H), 8.35 (d, 1H) 12.24 (s, 1H); M/(−) 416.4 (M−H+).

Workup

  1. concentrationThe reaction was concentrated in vacuo
  2. dissolutionthe residue dissolved in ethyl acetate (30 ml)
  3. washwashed with HCl (2M, 30 ml) and water (30 ml)
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated in vacuo
  6. customto give the crude product which
  7. customwas triturated with a mixture of dichloromethane, ethyl acetate and hexane

Sources & evidence

ORD record
ord-188324d7df214e5da4edb5b21312741e
Source dataset
uspto-grants-2004_12
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US06833387B1

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes