Methyl iodide → HCID 57441134, compound

HRID 1517066Notes

Reaction equation

HRID 1517066 reaction equation
[CH3:1][O:2][C:3]([C:5]1[C:10]([Cl:11])=[CH:9][C:8](Cl)=[CH:7][N:6]=1)=[O:4].ClC1C(C(O)=O)=NC=C(Cl)C=1.IC.C(=O)([O-])[O-].[K+].[K+].[F:32][C:33]([F:44])([F:43])[C:34]1[CH:35]=[C:36](B(O)O)[CH:37]=[CH:38][CH:39]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.C(COC)OC>[CH3:1][O:2][C:3]([C:5]1[C:10]([Cl:11])=[CH:9][C:8]([C:38]2[CH:37]=[CH:36][CH:35]=[C:34]([C:33]([F:44])([F:43])[F:32])[CH:39]=2)=[CH:7][N:6]=1)=[O:4]

Participants

9

Reactant 6

HCID 6328Methyl iodideHCID 10796Cesium carbonateHCID 11430Potassium CarbonateHCID 2199893,5-Dichloro-2-pyridinecarboxylic acidHCID 225523Methyl 3,5-dichloropicolinateHCID 27343883-(Trifluoromethyl)phenylboronic acid

Product 1

HCID 57441134HCID 57441134, compoundYield 20%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

To a degassed solution of 10.48 g (50.9 mmol) of 3,5-dichloro-pyridine-2-carboxylic acid methyl ester [prepared in analogy to the procedure described for the preparation of intermediate 5A from 3,5-dichloro-pyridine-2-carboxylic acid and iodomethane, potassium carbonate in DMF] in 400 ml of dimethoxyethane were added 14.49 g (76.3 mmol) of 3-(trifluoromethyl)phenyl boronic acid and 49.73 g (152.6 mmol) of caesium carbonate. While stirring, 0.77 g (1.50 mmol) of [(t-Bu)2P(OH)]2PdCl2 (POPd) was added and the reaction mixture was stirred at reflux for 7 hours. It was then cooled down to RT, poured into crashed ice and extracted twice with EtOAc; the organic phases were washed with water, dried over magnesium sulfate, filtered and evaporated. The residue was purified by flash column chromatography (heptane/EtOAc 98:2 to 1:1) to give 3.22 g (20%) of 3-chloro-5-(3-trifluoromethyl-phenyl)-pyridine-2-carboxylic acid methyl ester as light yellow oil; [MS: 316.0 (MH+, 1Cl)] and 2.80 g (12.9%) of 3,5-bis-(3-trifluoromethyl-phenyl)-pyridine-2-carboxylic acid methyl ester as light yellow solid; [MS: 426.1 (MH+)] and 3.21 g (20.0%) of 5-chloro-3-(3-trifluoromethyl-phenyl)-pyridine-2-carboxylic acid methyl ester as light yellow oil. [MS: 316.0 (MH+, 1Cl)].

Workup

  1. stirringthe reaction mixture was stirred
  2. temperatureat reflux for 7 hours
  3. additionpoured
  4. extractionextracted twice with EtOAc
  5. washthe organic phases were washed with water
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. customevaporated
  9. customThe residue was purified by flash column chromatography (heptane/EtOAc 98:2 to 1:1)

Sources & evidence

ORD record
ord-fc486cb8332645cd9bb5720d0c1abdb0
Source dataset
uspto-grants-2012_07
Patent number
US08227613B2

Reaction notes

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