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

HRID 2278597Notes

Reaction equation

HRID 2278597 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 it is then allowed to warm up to ambient temperature. After 2 hours, the reaction mixture is poured into an Erlenmeyer flask containing ice-cold water (200 ml) and then the pH is 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, the characteristics of which are the following:

Workup

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

Sources & evidence

ORD record
ord-2fe060e40a43404c9465eb5e114f0334
Source dataset
uspto-grants-2015_09
Patent number
US09133168B2

Reaction notes

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