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

HRID 2307930Notes

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]

Participants

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

concentrationThe reaction was concentrated in vacuo
dissolutionthe residue dissolved in ethyl acetate (30 ml)
washwashed with HCl (2M, 30 ml) and water (30 ml)
dry with materialdried (MgSO4)
concentrationconcentrated in vacuo
customto give the crude product which
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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