4-Fluorobenzaldehyde → 5-Fluoro-6-(4-fluoro-benzylamino)-1,3-dihydro-indol-2-one

HRID 2191405Notes

Reaction equation

HRID 2191405 reaction equation
[NH2:1][C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][C:7](=[O:11])[NH:8]2)=[CH:4][C:3]=1[F:12].[F:13][C:14]1[CH:21]=[CH:20][C:17]([CH:18]=O)=[CH:16][CH:15]=1.[BH4-].[Na+]>C(O)C>[F:12][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][C:2]=1[NH:1][CH2:18][C:17]1[CH:20]=[CH:21][C:14]([F:13])=[CH:15][CH:16]=1)[NH:8][C:7](=[O:11])[CH2:6]2

Participants

5

Reactant 3

HCID 680234-FluorobenzaldehydeHCID 4311764Sodium borohydrideHCID 101035046-Amino-5-fluoroindolin-2-one

Product 1

HCID 592500565-Fluoro-6-(4-fluoro-benzylamino)-1,3-dihydro-indol-2-oneYield 45%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

6-Amino-5-fluoro-1,3-dihydro-indol-2-one 3d (2.26 g, 13.6 mmol) was dissolved in 40 ml of ethanol under stirring at room temperature, the resulting solution was cooled down to 0° C. in an ice-water bath, and added with 4-fluoro-benzaldehyde (1.5 ml, 13.6 mmol) to the solution. Upon completion of the addition, the resulting solution was stirred for 1 hour at room temperature, added with sodium borohydride (1.08 g, 28.5 mmol) and heated to reflux for 18 hours. After thin lay chromatography showed the disappearance of starting materials, the reaction mixture was naturally cooled down to room temperature, added with ice water and lots of precipitates were formed, filtered and washed with water (50 ml×3). The residue was purified by silica gel column chromatography to obtain the title compound 5-fluoro-6-(4-fluoro-benzylamino)-1,3-dihydro-indol-2-one 3e (1.67 g, yield 45%) as a white solid.

Workup

  1. temperaturethe resulting solution was cooled down to 0° C. in an ice-water bath
  2. additionUpon completion of the addition
  3. stirringthe resulting solution was stirred for 1 hour at room temperature
  4. temperatureheated
  5. temperatureto reflux for 18 hours
  6. temperaturethe reaction mixture was naturally cooled down to room temperature
  7. customof precipitates
  8. customwere formed
  9. filtrationfiltered
  10. washwashed with water (50 ml×3)
  11. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-b02a57ce64874e25978c06f321b6be14
Source dataset
uspto-grants-2012_12
Patent number
US08329682B2

Reaction notes

Loading…