Water → Methyl 5-(3-(trifluoromethyl)phenyl)nicotinate

HRID 383792Notes

Reaction equation

HRID 383792 reaction equation
Br[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8].[F:12][C:13]([F:24])([F:23])[C:14]1[CH:15]=[C:16](B(O)O)[CH:17]=[CH:18][CH:19]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].O>O1CCOCC1.CCOC(C)=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:12][C:13]([F:24])([F:23])[C:14]1[CH:19]=[C:18]([C:2]2[CH:3]=[N:4][CH:5]=[C:6]([CH:11]=2)[C:7]([O:9][CH3:10])=[O:8])[CH:17]=[CH:16][CH:15]=1

Participants

8

Reactant 4

HCID 962WaterHCID 62657Potassium Phosphate, TribasicHCID 699336Methyl 5-bromopyridine-3-carboxylateHCID 27343883-(Trifluoromethyl)phenylboronic acid

Product 1

HCID 20099856Methyl 5-(3-(trifluoromethyl)phenyl)nicotinateYield 86.8%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

Methyl 5-bromonicotinate (168.2 mg), 3-trifluoromethylbenzeneboronic acid (165.6 mg), K3PO4 (378.5 mg) and Pd(PPh3)4 (92.2 mg) was mixed in dioxane (5 ml). To the suspension was added water (0.25 ml). And the mixture was heated to 100° C. under stirring. After 6 hours, the mixture was cooled to room temperature and was diluted with EtOAc. The insoluble material was filtered off and washed with EtOAc. The filtrate was poured into saturated aqueous solution of NaHCO3 and extracted with EtOAc. The extract was washed with brine, dried over MgSO4 and concentrated. The residue was purified with silica gel column chromatography (eluent: hexane/EtOAc=94/6˜50/50) to give methyl 5-[3-(trifluoromethyl)phenyl]nicotinate (190.1 mg) as a pale yellow solid.

Workup

  1. temperaturethe mixture was cooled to room temperature
  2. filtrationThe insoluble material was filtered off
  3. washwashed with EtOAc
  4. additionThe filtrate was poured into saturated aqueous solution of NaHCO3
  5. extractionextracted with EtOAc
  6. washThe extract was washed with brine
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated
  9. customThe residue was purified with silica gel column chromatography (eluent: hexane/EtOAc=94/6˜50/50)

Sources & evidence

ORD record
ord-c634841e824d43c59b475d3edb106302
Source dataset
uspto-grants-2013_02
Patent number
US08367690B2

Reaction notes

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