Sodium Carbonate → Methyl 5-(4-chloro-3-methylphenyl)-6-(2,2,2-trifluoroethoxy)nicotinate

HRID 1025979

Reaction equation

HRID 1025979 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:6]=[N:7][C:8]([O:12][CH2:13][C:14]([F:17])([F:16])[F:15])=[C:9](Br)[CH:10]=1)=[O:4].[Cl:18][C:19]1[CH:24]=[CH:23][C:22](B(O)O)=[CH:21][C:20]=1[CH3:28].C([O-])([O-])=O.[Na+].[Na+].C(OCC)(=O)C.CCCCCCC>CS(C)=O.O>[Cl:18][C:19]1[CH:24]=[CH:23][C:22]([C:9]2[C:8]([O:12][CH2:13][C:14]([F:17])([F:16])[F:15])=[N:7][CH:6]=[C:5]([CH:10]=2)[C:3]([O:2][CH3:1])=[O:4])=[CH:21][C:20]=1[CH3:28]

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 3786632(4-Chloro-3-methylphenyl)boronic acidHCID 21899848Ethylacetate heptaneHCID 66686828Methyl 5-bromo-6-(2,2,2-trifluoroethoxy)nicotinate

Product 1

HCID 66678833Methyl 5-(4-chloro-3-methylphenyl)-6-(2,2,2-trifluoroethoxy)nicotinateYield 106.4%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

5-Bromo-6-(2,2,2-trifluoroethoxy)-3-pyridinecarboxylic acid methyl ester (CAN 1211589-51-3; 4.0 g; 12.7 mmol) and 4-chloro-3-methylphenylboronic acid (CAN 161950-10-3; 3.26 g, 19.1 mmol) were combined in DMSO (100 mL) to give a white suspension. To this suspension was added, Na2CO3 (4.05 g, 38.2 mmol) in water (10 mL) and 1,1′-bis(diphenylphosphino)-ferrocene-palladium(II)dichloride dichloromethane complex (1.04 g, 1.27 mmol). The reaction mixture was heated to 80° C. and stirred for 2.5 h, cooled and poured into 200 mL ethyl acetate:heptane (1:1) and extracted with H2O (3×100 mL) and brine (1×150 ml). The aqueous layer was extracted with EtOAc:Heptane (1:1) (1×200 mL). The organic layers were combined, dried with Na2SO4 and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 70 g, 0% to 100% ethyl acetate in heptane) to yield 4.86 g (90%) of the title compound as light red solid; MS (EI): 360.1 (M+H)+.

Workup

  1. customto give a white suspension
  2. additionTo this suspension was added
  3. temperaturecooled
  4. extractionextracted with H2O (3×100 mL) and brine (1×150 ml)
  5. extractionThe aqueous layer was extracted with EtOAc:Heptane (1:1) (1×200 mL)
  6. dry with materialdried with Na2SO4
  7. concentrationconcentrated in vacuo
  8. customThe crude material was purified by flash chromatography (silica gel, 70 g, 0% to 100% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-43de923bfba64564ab3d3dc8a5ef33ec
Source dataset
uspto-grants-2014_05
Patent number
US08729105B2

Linked notes

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