Ammonia → 4-bromo-2-methyl-2,3-dihydro-1H-indole

HRID 2278517Notes

Reaction equation

HRID 2278517 reaction equation
C([BH3-])#N.[Na+].[Br:5][C:6]1[CH:14]=[CH:13][CH:12]=[C:11]2[C:7]=1[CH:8]=[C:9]([CH3:15])[NH:10]2.N>C(O)(=O)C>[Br:5][C:6]1[CH:14]=[CH:13][CH:12]=[C:11]2[C:7]=1[CH2:8][CH:9]([CH3:15])[NH:10]2

Participants

5

Reactant 3

HCID 222AmmoniaHCID 5003444Sodium cyanoborohydrideHCID 218145664-Bromo-2-methyl-1H-indole

Product 1

HCID 107272374-bromo-2-methyl-2,3-dihydro-1H-indole

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
14 °C

Procedure

7.99 g of sodium cyanoborohydride are gradually added to a solution of 8.90 g of 4-bromo-2-methylindole (which can be prepared according to patent US2010/160647 A1, 2010) in 310 ml of acetic acid under argon cooled to a temperature of about 14° C. The reaction mixture is stirred at a temperature of about 14° C. for 15 minutes, and is then left to warm back up to ambient temperature. After 2 hours, the reaction mixture is poured into an Erlenmayer flask containing ice-cold water (200 ml) and the pH is then brought to 9 with an aqueous ammonia solution. The reaction medium is extracted with dichloromethane (2×200 ml) and then the organic phases are combined, washed with water, dried over magnesium sulfate, filtered, and then concentrated to dryness under reduced pressure. After purification of the residue by silica column chromatography, elution being carried out with a mixture of heptane and ethyl acetate (90/10), 5.92 g of 4-bromo-2-methylindoline are obtained.

Workup

  1. waitis then left
  2. temperatureto warm back up to ambient temperature
  3. waitAfter 2 hours
  4. additionthe reaction mixture is poured into an Erlenmayer flask
  5. extractionThe reaction medium is extracted with dichloromethane (2×200 ml)
  6. washwashed with water
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated to dryness under reduced pressure
  10. customAfter purification of the residue
  11. washby silica column chromatography, elution
  12. additionbeing carried out with a mixture of heptane and ethyl acetate (90/10), 5.92 g of 4-bromo-2-methylindoline
  13. customare obtained

Sources & evidence

ORD record
ord-a2977d4f20734792a17245d6a9a822cd
Source dataset
uspto-grants-2015_09
Patent number
US09133168B2

Reaction notes

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