Dimethylformamide → HCID 86672719, compound

HRID 2369924Notes

Reaction equation

HRID 2369924 reaction equation
P(Cl)(Cl)(Cl)=O.[CH3:6][O:7][C:8]1[CH:27]=[CH:26][C:11]([CH2:12][N:13]2[C:21]3[CH:20]=[CH:19][CH:18]=[C:17]([C:22]([O:24][CH3:25])=[O:23])[C:16]=3[CH:15]=[CH:14]2)=[CH:10][CH:9]=1.[OH-].[Na+].CN([CH:33]=[O:34])C>>[CH:33]([C:15]1[C:16]2[C:17]([C:22]([O:24][CH3:25])=[O:23])=[CH:18][CH:19]=[CH:20][C:21]=2[N:13]([CH2:12][C:11]2[CH:10]=[CH:9][C:8]([O:7][CH3:6])=[CH:27][CH:26]=2)[CH:14]=1)=[O:34]

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 14798Sodium HydroxideHCID 24813Phosphorus oxychlorideHCID 66899007HCID 66899007, compound

Product 1

HCID 86672719HCID 86672719, compoundYield 93%

Conditions

Temperature
0 °C

Procedure

Phosphorus oxychloride (7.74 ml, 84.6 mmol) was added slowly to ice-cold DMF (200 mL) and the resulting mixture was stirred at 0° C. for 1 h. To this mixture was added a solution of methyl 1-(4-methoxybenzyl)-1H-indole-4-carboxylate (16.6 g, 56.4 mmol) from Step A above in DMF (100 mL) and the mixture was stirred for 2 h. The reaction mixture was poured into an ice/water mixture and the pH was adjusted to 7 by adding 1 N NaOH. The compound was extracted with ethyl acetate (3×500 mL) and the combined organic layers were washed with water (4×250 mL) and brine (4×250 mL), dried (Na2SO4), filtered, and concentrated under reduced pressure. The crude material was purified by silica gel chromatography (ethyl acetate/hexanes: 20-40%) to afford methyl 3-formyl-1-(4-methoxybenzyl)-1H-indole-4-carboxylate (16.7 g, 93%) as an off-white solid: 1H NMR (500 MHz, CDCl3) δ 10.48 (s, 1H), 7.99 (s, 1H), 7.85 (dd, J=10.0, 5.0 Hz, 1H), 7.55 (dd, J=10.0, 5.0 Hz, 1H), 7.30 (t, J=10.0 Hz, 1H), 7.12 (d, J=10.0 Hz, 2H), 6.86 (d, J=10.0 Hz, 2H), 5.31 (s, 2H), 3.99 (s, 3H), 3.71 (s, 3H); MS (ESI+) m/z 324 (M+H).

Workup

  1. stirringthe mixture was stirred for 2 h
  2. extractionThe compound was extracted with ethyl acetate (3×500 mL)
  3. washthe combined organic layers were washed with water (4×250 mL) and brine (4×250 mL)
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe crude material was purified by silica gel chromatography (ethyl acetate/hexanes: 20-40%)

Sources & evidence

ORD record
ord-5d6def394563404e92a6ff675cae2eea
Source dataset
uspto-grants-2014_04
Patent number
US08710046B2

Reaction notes

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