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

HRID 574229Notes

Reaction equation

HRID 574229 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), then p-toluenesulfonic acid (TsOH) (0.115 g, 0.669 mmol) and acetonylacetone (0.941 ml, 8.03 mmol) was added. The reaction mixture was heated at reflux for 2 hrs 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 200 ml EtOAc, washed with NaHCO3 (50 ml), dried (MgSO4) and concentrated in vacuo to give a brown solid; 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 hrs
  3. concentrationThe resulting dark red/black solution was concentrated in vacuo
  4. customto remove toluene
  5. additionthe crude residue diluted with 200 ml EtOAc
  6. washwashed with NaHCO3 (50 ml)
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated in vacuo
  9. customto give a brown solid

Sources & evidence

ORD record
ord-96aaeaa3676d4568943add4e1022f110
Source dataset
uspto-grants-2015_05
Patent number
US09034879B2

Reaction notes

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