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

HRID 2278600Notes

Reaction equation

HRID 2278600 reaction equation
C([BH3-])#N.[Na+].[F: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.O.N>C(O)(=O)C>[F: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

6

Reactant 4

HCID 222AmmoniaHCID 962WaterHCID 5003444Sodium cyanoborohydrideHCID 224900334-Fluoro-2-methyl-1h-indole

Product 1

HCID 573882254-fluoro-2-methyl-2,3-dihydro-1H-indoleYield 75.3%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
14 °C

Procedure

3.63 g of sodium cyanoborohydride are gradually added to a solution of 2.87 g of 4-fluoro-2-methylindole in 98 ml of acetic acid under argon cooled to a temperature of about 14° C. The reaction mixture is allowed to warm up to ambient temperature. After 2 hours, the reaction mixture is poured into a mixture of water and ice, and is then treated with a 28% aqueous ammonia solution until the pH is 9. The mixture is then extracted twice with dichloromethane. The organic phases are combined, dried over anhydrous magnesium sulfate, filtered, and then concentrated to dryness under reduced pressure. The residue is purified on a 300 g silica column, elution being carried out with a 100/0 to 90/10 v/v heptane/ethyl acetate gradient. 2.19 g of 4-fluoro-2-methyl-2,3-dihydro-1H-indole are thus obtained in the form of a colorless oil, the characteristics of which are the following:

Workup

  1. temperatureto warm up to ambient temperature
  2. extractionThe mixture is then extracted twice with dichloromethane
  3. dry with materialdried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated to dryness under reduced pressure
  6. customThe residue is purified on a 300 g silica column, elution

Sources & evidence

ORD record
ord-30e6186d36a04c3f862e435bd22d46f7
Source dataset
uspto-grants-2015_09
Patent number
US09133168B2

Reaction notes

Loading…