p-Toluenesulfonic acid → HCID 58442369, compound

HRID 444926

Reaction equation

HRID 444926 reaction equation
[CH3:1][O:2][C:3]([C:5]1[C:10]([NH2:11])=[CH:9][C:8]([C:12]([F:15])([F:14])[F:13])=[C:7]([Br:16])[N:6]=1)=[O:4].[C:17]1(C)[CH:22]=[CH:21][C:20](S(O)(=O)=O)=[CH:19][CH:18]=1.C(CC(=O)C)C(C)=O>C1(C)C=CC=CC=1>[CH3:1][O:2][C:3]([C:5]1[C:10]([N:11]2[C:19]([CH3:20])=[CH:18][CH:17]=[C:22]2[CH3:21])=[CH:9][C:8]([C:12]([F:15])([F:13])[F:14])=[C:7]([Br:16])[N:6]=1)=[O:4]

Participants

5

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 80352,5-HexanedioneHCID 58964428Methyl 3-amino-6-bromo-5-(trifluoromethyl)picolinate2×

Product 1

HCID 58442369HCID 58442369, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

3-Amino-6-bromo-5-trifluoromethyl-pyridine-2-carboxylic acid methyl ester (Intermediate A4) (2 g, 6.69 mmol) was suspended in toluene (8 ml), and treated with p-toluenesulfonic acid (TsOH) (0.115 g, 0.669 mmol) and acetonylacetone (0.941 ml, 8.03 mmol). The reaction mixture was heated at reflux for 2 hours (using Dean-Stark apparatus) and allowed to cool to RT overnight. The resulting dark red/black solution was concentrated in vacuo to remove toluene and the crude residue diluted with EtOAc (200 ml), washed with NaHCO3 (50 ml), dried (MgSO4) and concentrated in vacuo to give a brown solid. Purification of the solid by chromatography on silica eluting with EtOAc/iso-hexane afforded the title compound; LC-MS Rt=5.58 min [M+H]+ 377/379 (Method 10 minLC_v002).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux for 2 hours (using Dean-Stark apparatus)
  3. concentrationThe resulting dark red/black solution was concentrated in vacuo
  4. customto remove toluene
  5. additionthe crude residue diluted with EtOAc (200 ml)
  6. washwashed with NaHCO3 (50 ml)
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated in vacuo
  9. customto give a brown solid
  10. customPurification of the solid by chromatography on silica eluting with EtOAc/iso-hexane

Sources & evidence

ORD record
ord-c838c0491ae14cfeb76f34152d3ff06c
Source dataset
uspto-grants-2013_07
Patent number
US08476269B2

Linked notes

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