Sodium Hydroxide → Methyl 6-bromo-1-(sec-butyl)-3-formyl-1H-indole-4-carboxylate

HRID 42508Notes

Reaction equation

HRID 42508 reaction equation
O=P(Cl)(Cl)Cl.[Br:6][C:7]1[CH:8]=[C:9]([C:20]([O:22][CH3:23])=[O:21])[C:10]2[CH:11]=[CH:12][N:13]([CH:16]([CH2:18][CH3:19])[CH3:17])[C:14]=2[CH:15]=1.NCC1[C:27](=[O:36])NC(C)=CC=1CCC.[OH-].[Na+]>CN(C=O)C.O>[Br:6][C:7]1[CH:8]=[C:9]([C:20]([O:22][CH3:23])=[O:21])[C:10]2[C:11]([CH:27]=[O:36])=[CH:12][N:13]([CH:16]([CH2:18][CH3:19])[CH3:17])[C:14]=2[CH:15]=1

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 24813Phosphorus oxychlorideHCID 671241403-(Aminomethyl)-6-methyl-4-propylpyridin-2(1H)-oneacetateHCID 67466396Methyl 6-bromo-1-(sec-butyl)-1H-indole-4-carboxylate

Product 1

HCID 78358290Methyl 6-bromo-1-(sec-butyl)-3-formyl-1H-indole-4-carboxylate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Procedure

POCl3 (8.3 g, 54.3 mmol) was added at 0° C. to anhydrous DMF (230 mL) in a round bottom flask and stirred for 30 min. Then a solution of methyl 6-bromo-1-sec-butyl-1H-indole-4-carboxylate, 5 (14 g, 45.3 mmol) in DMF (60 mL) was added to the reaction mixture at 0° C. and stirred at room temperature for 2.5 h. The reaction mixture was diluted with cold water, adjusted pH˜8 using with 2N NaOH solution and extracted with ethyl acetate (4×200 mL). The combined organic layer was washed with cold water (2×100 mL), brine (100 mL), dried over anhydrous Na2SO4 and concentrated under reduced pressure to afford desired product methyl 6-bromo-1-sec-butyl-3-formyl-1H-indole-4-carboxylate, 6 (15.2 g, 99%) as pale yellow solid. This was used as such in the next step without purification. 1H NMR (CDCl3, 400 MHz) δ (0.831-0.859 (m, 3H), 1.515-1.574 (d, J=6.8 Hz, 3H), 1.729-1.972 (m, 2H) 3.997 (s, 3H), 4.394-4.445 (m, 1H), 7.756 (d, J=1.2 Hz, 1H), 7.958 (d, J=2 Hz, 1H), 8.079 (s, 1H), 10.452 (s, 1H).

Workup

  1. stirringstirred at room temperature for 2.5 h
  2. extractionextracted with ethyl acetate (4×200 mL)
  3. washThe combined organic layer was washed with cold water (2×100 mL), brine (100 mL)
  4. dry with materialdried over anhydrous Na2SO4
  5. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-cd4707863ec24b39947a5b613e9739ab
Source dataset
uspto-grants-2013_09
Patent number
US08536179B2

Reaction notes

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