Ethyl Bromide → 4-Ethoxy-3-fluoroaniline

HRID 1620297Notes

Reaction equation

HRID 1620297 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[C:4]([F:9])[CH:3]=1.C([O-])([O-])=O.[Cs+].[Cs+].Br[CH2:17][CH3:18]>CN(C=O)C>[CH2:17]([O:8][C:5]1[CH:6]=[CH:7][C:2]([NH2:1])=[CH:3][C:4]=1[F:9])[CH3:18]

Participants

5

Reactant 3

HCID 6332Ethyl BromideHCID 10796Cesium carbonateHCID 2735918Phenol, 4-amino-2-fluoro-

Product 1

HCID 195992054-Ethoxy-3-fluoroanilineYield 18.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 4-amino-2-fluorophenol (2.15 g, 16.9 mmol) in dry DMF (60 mL) in a 100 mL round-bottomed flask equipped with a magnetic stirrer was added Cs2CO3 (10.6 g, 25.4 mmol) and the mixture was stirred for 10 min at RT before addition of bromoethane (1.5 mL, 20.3 mmol). The reaction mixture was then stirred for 7 h at RT, concentrated to dryness, and the residue was partitioned between CH2Cl2 (100 mL) and water (20 mL). The organic layer was washed with brine (20 mL), dried over Na2SO4, filtered and concentrated at 40° C. under vacuum. Purification by column chromatography (SiO2, eluent cyclohexane:EtOAc=100:0 to 88:12) gave 4-ethoxy-3-fluoroaniline SMA 44094 as a brown oil (480 mg, 18% yield).

Workup

  1. concentrationconcentrated to dryness
  2. customthe residue was partitioned between CH2Cl2 (100 mL) and water (20 mL)
  3. washThe organic layer was washed with brine (20 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated at 40° C. under vacuum
  7. customPurification by column chromatography (SiO2, eluent cyclohexane:EtOAc=100:0 to 88:12)

Sources & evidence

ORD record
ord-88faa515bcda4c8f8f7496abde401b6b
Source dataset
uspto-grants-2014_07
Patent number
US08772316B2

Reaction notes

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