4-Fluoroindole → 4-Fluoro-2,3-dihydro-1H-indole

HRID 880511Notes

Reaction equation

HRID 880511 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]=[CH:9][NH:10]2>C(O)(=O)C>[F:5][C:6]1[CH:14]=[CH:13][CH:12]=[C:11]2[C:7]=1[CH2:8][CH2:9][NH:10]2

Participants

4

Reactant 2

HCID 27745024-FluoroindoleHCID 5003444Sodium cyanoborohydride

Product 1

HCID 162444404-Fluoro-2,3-dihydro-1H-indoleYield 49.2%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

Sodium cyanoborohydride (1.86 g, 29.62 mmol) was added portion wise to a solution of 4-fluoro-1H-indole (2 g, 14.81 mmol) in acetic acid (20 mL) at 0° C. and stirred at ambient temperature for 2 h. The resulting mixture was concentrated in vacuo and partitioned between ethyl acetate (100 mL) and water (100 mL). The organic layer was separated and the aqueous layer was extracted with ethyl acetate (5×30 mL). The combined organic layers were then washed with water (5×20 mL), sodium bicarbonate solution (3×30 mL), brine (3×20 mL), dried over anhydrous sodium sulphate and concentrated in vacuo to give the crude product. Purification by column chromatography over neutral alumina using 5% ethyl acetate in hexane as eluent to afforded 4-fluoroindoline (1 g, 45%) as a brown liquid.

Workup

  1. concentrationThe resulting mixture was concentrated in vacuo
  2. custompartitioned between ethyl acetate (100 mL) and water (100 mL)
  3. customThe organic layer was separated
  4. extractionthe aqueous layer was extracted with ethyl acetate (5×30 mL)
  5. washThe combined organic layers were then washed with water (5×20 mL), sodium bicarbonate solution (3×30 mL), brine (3×20 mL)
  6. dry with materialdried over anhydrous sodium sulphate
  7. concentrationconcentrated in vacuo
  8. customto give the crude product
  9. customPurification by column chromatography over neutral alumina using 5% ethyl acetate in hexane as eluent

Sources & evidence

ORD record
ord-f53190a5a97942a4a38badef5e0f76a5
Source dataset
uspto-grants-2015_03
Patent number
US08993574B2

Reaction notes

Loading…