Boron tribromide → 3-bromo-4-chloro-N-(2-hydroxy-phenyl)-N-methyl-benzamide

HRID 1848572Notes

Reaction equation

HRID 1848572 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([CH:17]=[CH:18][C:19]=1[Cl:20])[C:5]([N:7]([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[O:15]C)[CH3:8])=[O:6].B(Br)(Br)Br>C(Cl)Cl>[Br:1][C:2]1[CH:3]=[C:4]([CH:17]=[CH:18][C:19]=1[Cl:20])[C:5]([N:7]([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[OH:15])[CH3:8])=[O:6]

Participants

4

Reactant 2

HCID 25134Boron tribromideHCID 686027713-bromo-4-chloro-N-(2-methoxy-phenyl)-N-methyl-benzamide

Product 1

HCID 686031173-bromo-4-chloro-N-(2-hydroxy-phenyl)-N-methyl-benzamideYield 93%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a cooled solution (−70° C.) of 3-bromo-4-chloro-N-(2-methoxy-phenyl)-N-methyl-benzamide (2 g, 5.64 mmol) in DCM (20 mL), BBr3 (1.7 mL, 18 mmol) was added drop-wise over a 20 minute period. The reaction temperature was allowed to increase to room temperature over 12 hrs until completion of the reaction. After concentration in vacuo the mixture was partitioned between DCM and water. 1N NaOH was added to increase pH to ˜5. The organic layer was separated and washed with brine and dried over Na2SO4. Concentration and purification by silica gel column chromatography eluting with hexane/ethyl acetate (4/1 with gradient up to 3/2) yielded 3-bromo-4-chloro-N-(2-hydroxy-phenyl)-N-methyl-benzamide (1.78 g, 93%). MS [M+H]+: 341.9; tR=2.56 min. (method 1)

Workup

  1. concentrationAfter concentration in vacuo the mixture
  2. customwas partitioned between DCM and water
  3. addition1N NaOH was added
  4. temperatureto increase pH to ˜5
  5. customThe organic layer was separated
  6. washwashed with brine
  7. dry with materialdried over Na2SO4
  8. concentrationConcentration and purification by silica gel column chromatography
  9. washeluting with hexane/ethyl acetate (4/1 with gradient up to 3/2)

Sources & evidence

ORD record
ord-47309abad0a84c52a1298edaf421e8bf
Source dataset
uspto-grants-2015_02
Patent number
US08952161B2

Reaction notes

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