Ethyl Acetate → HCID 59226464, compound

HRID 2192654Notes

Reaction equation

HRID 2192654 reaction equation
[F:1][C:2]1[C:7](OS(C(F)(F)F)(=O)=O)=[CH:6][CH:5]=[C:4]([F:16])[C:3]=1[C:17]1[N:22]=[C:21]([C:23]([O:25]C)=[O:24])[CH:20]=[CH:19][C:18]=1[F:27].[CH3:28]B(O)O.C(=O)([O-])[O-].[K+].[K+].C(OCC)(=O)C>O1CCOCC1.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:1][C:2]1[C:7]([CH3:28])=[CH:6][CH:5]=[C:4]([F:16])[C:3]=1[C:17]1[N:22]=[C:21]([C:23]([OH:25])=[O:24])[CH:20]=[CH:19][C:18]=1[F:27]

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 139377Methylboronic AcidHCID 59226470HCID 59226470, compound

Product 1

HCID 59226464HCID 59226464, compoundYield 97%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution methyl 6-(2,6-difluoro-3-(trifluoromethylsulfonyloxy)phenyl)-5-fluoropicolinate (1.0 equiv.) in dioxane and water (10:1, 0.15 M) was added methyl boronic acid (3.0 equiv.) and potassium carbonate (3.0 equiv.). The reaction was degassed with nitrogen for 10 min, then Pd(PPh3)4 (0.1 equiv.) was added to the solution and heated to 100° C. for 3 hours. LC/MS of the reaction at this point indicated complete conversion to the carboxylic acid product (M+H=268). Cooled to room temperature and added water and ethyl acetate. The two layers were separated, the aqueous phase was acidified with concentrated HCl to pH=1 and extracted with ethyl acetate. The organic phase was dried with sodium sulfate, filtered, and concentrated under vacuo to give 6-(2,6-difluoro-3-methylphenyl)-5-fluoropicolinic acid as a clear oil in 97% yield. LC/MS=268.1 (M+H), Rt=0.82 min.

Workup

  1. customThe reaction was degassed with nitrogen for 10 min
  2. customLC/MS of the reaction at this point
  3. temperatureCooled to room temperature
  4. customThe two layers were separated
  5. extractionextracted with ethyl acetate
  6. dry with materialThe organic phase was dried with sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under vacuo

Sources & evidence

ORD record
ord-aab1f985acc54648a2d77b4c50f2b9aa
Source dataset
uspto-grants-2012_12
Patent number
US08329732B2

Reaction notes

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