Water → HCID 22394611, compound

HRID 1623532Notes

Reaction equation

HRID 1623532 reaction equation
[CH3:1][N:2]1[C:10]2[C:5](=[C:6]([CH3:11])[CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3]1.[OH2:12].[Br-:13].[K+].BrBr>C(O)(C)(C)C.ClCCl.C(=O)(O)[O-].[Na+].S([O-])([O-])(=O)=S.[Na+].[Na+].C(O)(=O)C.[Zn]>[Br:13][C:7]1[C:6]([CH3:11])=[C:5]2[C:10](=[CH:9][CH:8]=1)[N:2]([CH3:1])[C:3](=[O:12])[CH2:4]2

Participants

11

Reactant 4

HCID 962Water2×HCID 24408Bromine2×HCID 253877Potassium BromideHCID 5893891,4-Dimethylindole2×

Product 1

HCID 22394611HCID 22394611, compound

Reagents, catalysts & solvents 6

HCID 23994ZincCatalystHCID 176Acetic AcidSolventHCID 6344DichloromethaneSolventHCID 6386tert-ButanolSolventHCID 24477Sodium ThiosulfateSolventHCID 516892Sodium BicarbonateSolvent

Procedure

To a solution of 1,4-dimethyl-1H-indole, (200 mg, 1.38 mmol) in tert-butanol (8 mL) was added water (4 mL) and the mixture was put at 50° C. In a separate flask was added potassium bromide (1.6 g, 13.8 mmol) followed by water (11 mL) and bromine (0.36 mL, 6.9 mmol). Next the bromine solution (8 was added dropwise to the 1,4-dimethyl-1H-indole mixture. After the addition was complete the temperature of the reaction was elevated to 70° C. for 30 min. The reaction was cooled to room temperature and diluted with dichloromethane and saturated aqueous sodium bicarbonate. The solution was then further diluted with saturated aqueous sodium thiosulfate. The layers were separated and the aqueous layer was extracted two additional times with dichloromethane. The organic extracts were combined, dried over anhydrous sodium sulfate, filtered and concentrated. The resulting solid was filtrated with diethyl ether and one half of the solid, by weight, was then dissolved in acetic acid (2.5 Zinc dust (62 mg, 0.94 mmol) was then added. After 10 minutes the reaction mixture was filtered through a pad of Celite® and diluted with dichloromethane. The resulting solution was cooled to 0° C. and neutralized via the cautious addition of 2 N aqueous sodium hydroxide and saturated aqueous sodium bicarbonate. The resulting layers were separated and the aqueous layer was extracted two additional times with dichloromethane. The combined organic layers were dried over anhydrous sodium sulfate, filtered and concentrated. The resulting residue was purified by silica gel flash chromatography (ethyl acetate-heptane 15 to 80%) to afford 5-bromo-1,4-dimethyl-1,3-dihydro-indol-2-one; 1H NMR (400 MHz, CDCl3) δ ppm 2.32 (s, 3H), 3.19 (s, 3H), 3.47 (s, 2H), 6.56 (d, J=8.1 Hz, 1H), 7.48 (d, J=8.1 Hz, 1H).

Workup

  1. customwas put at 50° C
  2. additionAfter the addition
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted two additional times with dichloromethane
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. filtrationThe resulting solid was filtrated with diethyl ether and one half of the solid, by weight
  9. additionwas then added
  10. filtrationAfter 10 minutes the reaction mixture was filtered through a pad of Celite®
  11. additiondiluted with dichloromethane
  12. temperatureThe resulting solution was cooled to 0° C. and neutralized via the cautious addition of 2 N aqueous sodium hydroxide and saturated aqueous sodium bicarbonate
  13. customThe resulting layers were separated
  14. extractionthe aqueous layer was extracted two additional times with dichloromethane
  15. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
  16. filtrationfiltered
  17. concentrationconcentrated
  18. customThe resulting residue was purified by silica gel flash chromatography (ethyl acetate-heptane 15 to 80%)

Sources & evidence

ORD record
ord-a00c5a4b34094070a4a53dba0b08aa03
Source dataset
uspto-grants-2014_07
Patent number
US08778972B2

Reaction notes

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