p-Toluenesulfonic acid → 6-Bromo-3-(2,5-dimethyl-pyrrol-1-yl)-5-trifluoromethyl-pyridine-2-carboxylic acid methyl ester

HRID 2202511Notes

Reaction equation

HRID 2202511 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 584423696-Bromo-3-(2,5-dimethyl-pyrrol-1-yl)-5-trifluoromethyl-pyridine-2-carboxylic acid methyl ester

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 10minLC_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-795baecdb83c4c1cb890056e66775de0
Source dataset
uspto-grants-2016_06
Patent number
US09365552B2

Reaction notes

Loading…