Bromine → 2-(Benzyloxy)-4-bromo-6-fluoroaniline

HRID 889241Notes

Reaction equation

HRID 889241 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([F:15])[C:10]=1[NH2:16])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Br:17]Br>CO.CC(O)=O>[CH2:1]([O:8][C:9]1[CH:14]=[C:13]([Br:17])[CH:12]=[C:11]([F:15])[C:10]=1[NH2:16])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 24408BromineHCID 15219197HCID 15219197, compound

Product 1

HCID 684315652-(Benzyloxy)-4-bromo-6-fluoroaniline

Reagents, catalysts & solvents 1

HCID 10129899Acetic acid methanolSolvent2×

Procedure

To a solution of 2-benzyloxy-6-fluorophenylamine (7.29 g, 33.6 mmol) in MeOH/HOAc (3:1 v/v, 30 mL) at 0° C. is added bromine (2.2 mL, 47 mmol) in MeOH/HOAc (3:1 v/v, 4 mL) drop wise. After it is stirred for 4 h, the reaction is completed by LC/MS. The reaction mixture is concentrated, and the residue is stirred with EtOAc and 1N NaOH to dissolve solid. Additional base is added to make the aqueous alkaline, and then EtOAc layer is separated. The organic phase is washed with brine, dried and filtered. The concentrated residue is purified to give the title compound: 1H NMR (CDCl3) 7.39 (m, 5H), 6.86 (dd, 1H, J=9.8, 2.0 Hz), 6.81 (m, 1H), 5.05 (s, 2H), 3.77 (br s, 2H); MS (M+H)+=296, 298.

Workup

  1. concentrationThe reaction mixture is concentrated
  2. stirringthe residue is stirred with EtOAc and 1N NaOH
  3. dissolutionto dissolve solid
  4. additionAdditional base is added
  5. customEtOAc layer is separated
  6. washThe organic phase is washed with brine
  7. customdried
  8. filtrationfiltered
  9. customThe concentrated residue is purified

Sources & evidence

ORD record
ord-40de82d4583a4eb6abad515e88615384
Source dataset
uspto-grants-2012_08
Patent number
US08252820B2

Reaction notes

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