o-(Methylamino)phenol → 3-bromo-4-chloro-N-(2-hydroxy-phenyl)-N-methyl-benzamide

HRID 1485990Notes

Reaction equation

HRID 1485990 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[Cl:11])[C:5](Cl)=[O:6].[CH3:12][NH:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[OH:20].C([O-])(O)=O.[Na+]>C(#N)C.O>[Br:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[Cl:11])[C:5]([N:13]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[OH:20])[CH3:12])=[O:6]

Participants

6

Reactant 3

HCID 69138o-(Methylamino)phenolHCID 516892Sodium BicarbonateHCID 202297303-Bromo-4-chlorobenzoyl chloride

Product 1

HCID 686031173-bromo-4-chloro-N-(2-hydroxy-phenyl)-N-methyl-benzamideYield 56.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent2×

Procedure

3-Bromo-4-chloro-benzoyl chloride (Step 2A, 106.9 mmol) in acetonitrile (300 mL) was added dropwise over 30 minutes to a vigorously stirring solution of 2-methylamino-phenol (15.1 g, 122.9 mmol) and NaHCO3 (18.0 g, 213.7 mmol) in acetonitrile (200 mL) and water (200 mL). The mixture was stirred for additional 1 h and then concentrated to remove acetonitrile. The solid was filtered, washed with HCl (1N, 600 mL) and water (500 mL), and dried. The solid was dissolved in dichloromethane (500 mL) and n-butylamine (20 mL) was added. The mixture was stirred at rt for 16 hrs and concentrated. The residue was partially purified via silica gel flash chromatography (eluting with 20% to 35% ethyl acetate in hexane) and then crystallized from hexane/ethyl acetate (75/25) to give 3-bromo-4-chloro-N-(2-hydroxy-phenyl)-N-methyl-benzamide (20.5 g) as a white solid. MS [M+H]+: 339.7/341.8; tR=2.19 min. (method 1)

Workup

  1. concentrationconcentrated
  2. customto remove acetonitrile
  3. filtrationThe solid was filtered
  4. washwashed with HCl (1N, 600 mL) and water (500 mL)
  5. customdried
  6. dissolutionThe solid was dissolved in dichloromethane (500 mL)
  7. additionn-butylamine (20 mL) was added
  8. stirringThe mixture was stirred at rt for 16 hrs
  9. concentrationconcentrated
  10. customThe residue was partially purified via silica gel flash chromatography (eluting with 20% to 35% ethyl acetate in hexane)
  11. customcrystallized from hexane/ethyl acetate (75/25)

Sources & evidence

ORD record
ord-5eb3fbff21ff43d19eedac8902d63297
Source dataset
uspto-grants-2016_08
Patent number
US09422310B2

Reaction notes

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