N-(3,5-difluorophenyl)formamide → 3,5-difluoro-N-methylaniline

HRID 594791Notes

Reaction equation

HRID 594791 reaction equation
[H-].[H-].[H-].[H-].[Li+].[Al+3].[F:7][C:8]1[CH:9]=[C:10]([NH:15][CH:16]=O)[CH:11]=[C:12]([F:14])[CH:13]=1>C1COCC1>[F:7][C:8]1[CH:9]=[C:10]([CH:11]=[C:12]([F:14])[CH:13]=1)[NH:15][CH3:16]

Participants

4

Reactant 2

HCID 261761N-(3,5-difluorophenyl)formamideHCID 21226445Aluminium lithium hydride

Product 1

HCID 167203773,5-difluoro-N-methylanilineYield 86.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 3,5-difluoroaniline (5.0 g, 38.7 mmol) in HCOOH (15 mL) was heated to reflux for 4 h. The mixture was poured into ice-water and stirred for 0.5 h. The white solid was collected by filtration, and dried under vacuum to give 4.8 g (79%) of crude N-(3,5-difluorophenyl)formamide. To the solution of LiAlH4 (3.0 g, 78.9 mmol) in dry THF (50 mL) was added a solution of N-(3,5-difluorophenyl)formamide (4.8 g, 30.6 mmol) in dry THF (50 mL) at r.t. The mixture was stirred overnight and then quenched with addition of water (3.0 mL), aqueous 10% NaOH (3.0 mL), and water (9.0 ml). The reaction mixture was filtered and extracted with EtOAc. Organics were dried (Na2SO4), and concentrated to give 3.8 g (86%) of the title compound as a pale brown oil.

Workup

  1. customquenched with addition of water (3.0 mL), aqueous 10% NaOH (3.0 mL), and water (9.0 ml)
  2. filtrationThe reaction mixture was filtered
  3. extractionextracted with EtOAc
  4. dry with materialOrganics were dried (Na2SO4)
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-d4ea1fd34fb9487f941d5760e9d049cb
Source dataset
uspto-grants-2016_01
Patent number
US09242968B2

Reaction notes

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