Dimethylformamide → methyl 6-bromo-3-formyl-1-isopropyl-1H-indole-4-carboxylate

HRID 42504Notes

Reaction equation

HRID 42504 reaction equation
O=P(Cl)(Cl)Cl.[Br:6][C:7]1[CH:8]=[C:9]([C:19]([O:21][CH3:22])=[O:20])[C:10]2[CH:11]=[CH:12][N:13]([CH:16]([CH3:18])[CH3:17])[C:14]=2[CH:15]=1.[OH-].[Na+].CN([CH:28]=[O:29])C>O>[Br:6][C:7]1[CH:8]=[C:9]([C:19]([O:21][CH3:22])=[O:20])[C:10]2[C:11]([CH:28]=[O:29])=[CH:12][N:13]([CH:16]([CH3:18])[CH3:17])[C:14]=2[CH:15]=1

Participants

6

Reactant 4

HCID 6228Dimethylformamide2×HCID 14798Sodium HydroxideHCID 24813Phosphorus oxychlorideHCID 67466539methyl 6-bromo-1-isopropyl-1H-indole-4-carboxylate

Product 1

HCID 86677357methyl 6-bromo-3-formyl-1-isopropyl-1H-indole-4-carboxylateYield 91.3%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a stirred solution of DMF (1.04 lit) POCl3 (40.3 g, 263 mmol) was added at 0° C. and stirred for 20 min. Then methyl 6-bromo-1-isopropyl-1H-indole-4-carboxylate (65 g, 2119.5 mmol) in DMF (260 mL) was added to the reaction mixture at 0° C. The reaction mixture was stirred at room temperature for 3 h. Diluted the reaction mixture with cold water and adjusted PH˜8 using with 2N NaOH solution, extracted with ethylacetate (4×1 lit). The organic layer washed with cold water, brine solution, dried over anhydrous Na2SO4 and concentrated under reduced pressure to afford desired product methyl 6-bromo-3-formyl-1-isopropyl-1H-indole-4-carboxylate (65 g, 91.3%). 1H NMR (CDCl3, 400 MHz): δ 1.588 (d, 6H, J=6.8 Hz), 3.994 (s, 3H), 4.634-4.701 (m, 1H), 7.760 (d, 1H, J=1.6 Hz), 7.958 (d, 1H, J=1.6 Hz), 8.122 (s, 1H), 10.446 (s, 1H). LC-MS (ES+) m/z=324.02 (M+H)

Workup

  1. stirringThe reaction mixture was stirred at room temperature for 3 h
  2. extractionextracted with ethylacetate (4×1 lit)
  3. washThe organic layer washed with cold water, brine solution
  4. dry with materialdried over anhydrous Na2SO4
  5. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-31b6de1e950545bcbb691743fbd3ca51
Source dataset
uspto-grants-2013_09
Patent number
US08536179B2

Reaction notes

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