Dimethylformamide → 2-Isobutyl-5-methoxyindole-3-carboxaldehyde

HRID 570634Notes

Reaction equation

HRID 570634 reaction equation
P(Cl)(Cl)(Cl)=O.[CH2:6]([C:10]1[NH:11][C:12]2[C:17]([CH:18]=1)=[CH:16][C:15]([O:19][CH3:20])=[CH:14][CH:13]=2)[CH:7]([CH3:9])[CH3:8].CN(C)[CH:23]=[O:24]>>[CH2:6]([C:10]1[NH:11][C:12]2[C:17]([C:18]=1[CH:23]=[O:24])=[CH:16][C:15]([O:19][CH3:20])=[CH:14][CH:13]=2)[CH:7]([CH3:9])[CH3:8]

Participants

4

Reactant 3

HCID 6228Dimethylformamide2×HCID 24813Phosphorus oxychlorideHCID 10631992HCID 10631992, compound

Product 1

HCID 846946402-Isobutyl-5-methoxyindole-3-carboxaldehydeYield 94%

Procedure

Dimethylformamide (1 mL) was cooled to 0° C. Phosphorus oxychloride (0.5 mL) was added and the reaction mixture was stirred for 10 minutes. A solution of 2-isobutyl-5-methoxyindole (375 mg, 1.8 mmol) in dimethylformamide (2 mL) was added to the reaction mixture dropwise over 10 minutes. The solution was stirred for an additional 40 minutes. The reaction mixture was added to ice cold 1 N NaOH (35 mL) and stirred for 10 minutes. The precipitate was collected, washed with cold water (30 mL) and dried overnight in a vacuum desiccator set at 40° C. equipped to an oil driven vacuum pump yielding a tan solid (393 mg, 94%): TLC Rf 0.45 in 1:1 ethyl acetate/hexanes. Melting point=146-147° C. 1H NMR (600 MHz, CDCl3) δ 10.13 (s, 1H), 8.74 (s, 1H), 7.81 (d, 1H, J=2.5 Hz), 7.24-7.23 (d, 1H, J=8.7 Hz), 6.89-6.87 (dd, 1H, J1=8.7 Hz, J2=2.5 Hz), 3.87 (s, 3H), 2.93-2.92 (d, 2H, J=7.3 Hz), 2.11-2.05 (m, 1H), 1.02-1.01 (d, 6H, J=6.7 Hz); 13C NMR (150 MHz, CDCl3) δ 184.62, 156.48, 150.72, 129.69, 126.68, 115.22, 113.59, 111.55, 102.99, 55.80, 35.46, 30.08, 22.51. Elemental analysis calculated for C14H17NO2: C, 72.70; H, 7.41; N, 6.06. Found: C, 72.62; H, 7.52; N, 5.98.

Workup

  1. stirringThe solution was stirred for an additional 40 minutes
  2. stirringstirred for 10 minutes
  3. customThe precipitate was collected
  4. washwashed with cold water (30 mL)
  5. customdried overnight in a vacuum desiccator
  6. customset at 40° C.
  7. customequipped to an oil

Sources & evidence

ORD record
ord-f39e0d68b3494e40836978fe5514eeca
Source dataset
uspto-grants-2015_05
Patent number
US09023871B2

Reaction notes

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