Cesium fluoride → Methyl 6-(4-(trifluoromethyl)phenyl)nicotinate

HRID 1669236Notes

Reaction equation

HRID 1669236 reaction equation
[CH3:1][O:2][C:3](=[O:11])[C:4]1[CH:9]=[CH:8][C:7](Cl)=[N:6][CH:5]=1.[F:12][C:13]([F:24])([F:23])[C:14]1[CH:19]=[CH:18][C:17](B(O)O)=[CH:16][CH:15]=1.[F-].[Cs+]>O1CCOCC1>[CH3:1][O:2][C:3](=[O:11])[C:4]1[CH:9]=[CH:8][C:7]([C:17]2[CH:18]=[CH:19][C:14]([C:13]([F:24])([F:23])[F:12])=[CH:15][CH:16]=2)=[N:6][CH:5]=1

Participants

5

Reactant 3

HCID 25953Cesium fluorideHCID 254249Methyl 6-chloropyridine-3-carboxylateHCID 27343894-(Trifluoromethyl)phenylboronic acid

Product 1

HCID 21936350Methyl 6-(4-(trifluoromethyl)phenyl)nicotinateYield 90.4%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To an ambient temperature solution of 6-chloro-nicotinic acid methyl ester (12.4 g, 72 mmol) and 4-(trifluoromethyl)phenylboronic acid (15 g, 79 mmol) in dioxane (270 mL) is added CsF (38.3 g, 252 mmol) and the reaction mixture is degassed with nitrogen. PdCl2(dppf) (1.5 g) is added and the reaction mixture is heated to 100° C. over weekend. The reaction mixture was diluted with ethyl acetate, filtered through celite. The filtrate is concentrated. Purification of the crude product by column on silica gel (hexanes/ethyl acetate) gives 6-(4-trifluoromethyl-phenyl)-nicotinic acid methyl ester (18.3 g, 82.3% yield).

Workup

  1. customthe reaction mixture is degassed with nitrogen
  2. additionPdCl2(dppf) (1.5 g) is added
  3. additionThe reaction mixture was diluted with ethyl acetate
  4. filtrationfiltered through celite
  5. concentrationThe filtrate is concentrated
  6. customPurification of the crude product by column on silica gel (hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-87a0232dba88415ea117e62ec8580dac
Source dataset
uspto-grants-2011_08
Patent number
US07989457B2

Reaction notes

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