Indole → N-methoxy-N-methyl-3-(indol-5-yl)acrylamide

HRID 1836628

Reaction equation

HRID 1836628 reaction equation
[H-].[Na+].C(OP([CH2:11][C:12](=[O:17])[N:13]([O:15][CH3:16])[CH3:14])(=O)OCC)C.[NH:18]1[C:26]2[C:21](=[CH:22][C:23]([CH:27]=O)=[CH:24][CH:25]=2)[CH:20]=[CH:19]1.N1C2C(=CC=CC=2)C=C1>C1COCC1>[CH3:16][O:15][N:13]([CH3:14])[C:12](=[O:17])[CH:11]=[CH:27][C:23]1[CH:22]=[C:21]2[C:26](=[CH:25][CH:24]=1)[NH:18][CH:19]=[CH:20]2

Participants

6

Reactant 4

HCID 798IndoleHCID 24758Sodium hydrideHCID 589040Indole-5-carboxaldehydeHCID 2773719Diethyl (N-methoxy-N-methylcarbamoylmethyl)phosphonate

Product 1

HCID 73990728N-methoxy-N-methyl-3-(indol-5-yl)acrylamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of sodium hydride (0.44 g of a 60% suspension in mineral oil, 11 mmol) and diethyl-(N-methoxy-N-methyl-carbamoylmethyl)-phosphonate (3.0 g, 3 equiv.) in anhydrous THF was stirred at room temperature for 30 minutes. A solution of indole-5-carboxaldehyde (0.61 g, 4.18 mmol) was added dropwise to the mixture. The reaction was complete after 2 h after the addition of the starting indole. The mixture was quenched with water (50 ml), then diluted with ether. The organic layer was separated, dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo to give N-methoxy-N-methyl-3-(indol-5-yl)acrylamide as a yellow oil which solidified on standing to an off-white solid (1.53 g, quantitative yield. 1H NMR (CDCl3): δ8.55 (br, 1H), 7.87 (d, J=18.6 Hz, 1H), 7.85 (s, 1H), 7.38 (d, J=8.5 Hz, 1H), 7.25 (d, J=8.5 Hz, 1H), 7.23 (m, 1H), 7.0 (d, J=18.6 Hz, 1H), 6.58 (m, 1H), 3.78 (s, 3H), and 3.32 (s, 3H). FIMS: 229.1 (M−H)−, reverse-phase HPLC purity: 88%.

Workup

  1. waitThe reaction was complete after 2 h
  2. customThe mixture was quenched with water (50 ml)
  3. additiondiluted with ether
  4. customThe organic layer was separated
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-5a8ba1de68ef42b4918e2efe72737d08
Source dataset
uspto-grants-2004_08
Patent number
US06777437B2

Linked notes

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