Ethyl Acetate → 3-Amino-6-(2,4-dichloro-phenyl)-5-trifluoromethyl-pyridine-2-carboxylic acid methyl ester

HRID 444936

Reaction equation

HRID 444936 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)[N:6]=1)=[O:4].[Cl:17][C:18]1[CH:23]=[C:22]([Cl:24])[CH:21]=[CH:20][C:19]=1B(O)O.P([O-])([O-])([O-])=O.[K+].[K+].[K+].CCOC(C)=O>C1(C)C=CC=CC=1.O>[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]([C:21]2[CH:20]=[CH:19][C:18]([Cl:17])=[CH:23][C:22]=2[Cl:24])[N:6]=1)=[O:4]

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 62657Potassium Phosphate, TribasicHCID 2734659(2,4-Dichlorophenyl)boronic acidHCID 58964428Methyl 3-amino-6-bromo-5-(trifluoromethyl)picolinate2×

Product 1

HCID 673834083-Amino-6-(2,4-dichloro-phenyl)-5-trifluoromethyl-pyridine-2-carboxylic acid methyl ester

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

3-Amino-6-bromo-5-trifluoromethyl-pyridine-2-carboxylic acid methyl ester (Intermediate A4) (3 g, 10.03 mmol), 2,4-dichlorophenylboronic acid (2.297 g, 12.04 mmol), potassium phosphate (4.26 g, 20.06 mmol) and Fibrecat® 1034A (Johnson Matthey, polymer supported palladium complex) (500 mg, 10.03 mmol) were suspended in toluene (50 ml) and water (15 ml). The reaction mixture was heated to 110° C. under vigorous stirring for 3 hours. The mixture was allowed to cool to RT and EtOAc (100 ml) was added. The organic layer was separated and washed with brine (15 ml). MP-TMT (macroporous polystyrene-bound trimercaptotriazine, 3 g, Polymern labs) was added and stirred for 1 hour at RT. MgSO4 was added and the suspension filtered off. The filtrate was concentrated in vacuo and purification of the residue by reverse phase chromatography (130 g C18 column) eluting with water/MeOH afforded the title compound as a white solid; LS-MS Rt=1.55 mins [M+H]+ 365 (Method 2 minLC_v002).

Workup

  1. temperatureto cool to RT
  2. customThe organic layer was separated
  3. washwashed with brine (15 ml)
  4. additionMP-TMT (macroporous polystyrene-bound trimercaptotriazine, 3 g, Polymern labs) was added
  5. stirringstirred for 1 hour at RT
  6. additionMgSO4 was added
  7. filtrationthe suspension filtered off
  8. concentrationThe filtrate was concentrated in vacuo and purification of the residue by reverse phase chromatography (130 g C18 column)
  9. washeluting with water/MeOH

Sources & evidence

ORD record
ord-2da29150576f463b8e92df4e06ed1c0b
Source dataset
uspto-grants-2013_07
Patent number
US08476269B2

Linked notes

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