Potassium Carbonate → HCID 89676924, compound

HRID 2278258Notes

Reaction equation

HRID 2278258 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([CH2:8][N:9]2[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11][CH2:10]2)=[C:4]([F:22])[CH:3]=1.[CH3:23][C:24]1[CH:29]=[C:28](B(O)O)[CH:27]=[CH:26][N:25]=1.C(=O)([O-])[O-].[K+].[K+].O1CCOCC1>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.O>[F:22][C:4]1[CH:3]=[C:2]([C:28]2[CH:27]=[CH:26][N:25]=[C:24]([CH3:23])[CH:29]=2)[CH:7]=[CH:6][C:5]=1[CH2:8][N:9]1[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11][CH2:10]1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 41926642-Methylpyridine-4-boronic acidHCID 67328284HCID 67328284, compound

Product 1

HCID 89676924HCID 89676924, compoundYield 58.1%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
75 °C

Procedure

A 25 mL round-bottom flask was purged with and maintained under an inert atmosphere of nitrogen then charged with tert-butyl 4-[(4-bromo-2-fluorophenyl)methyl]piperazine-1-carboxylate (1.00 g, 2.68 mmol, 1.00 equiv), (2-methylpyridin-4-yl)boronic acid (0.737 g, 5.38 mmol, 2.01 equiv), Tetrakis(triphenylphosphine)palladium (0.311 g, 0.270 mmol, 0.10 equiv), potassium carbonate (1.10 g, 7.96 mmol, 2.97 equiv), dioxane (10 mL) and water (2 mL). The resulting solution was stirred overnight at 75° C. The reaction progress was monitored by LCMS. The reaction was then quenched by the addition of water (10 mL). The resulting solution was extracted with ethyl acetate (3×10 mL) and the organic layers were combined, washed with brine (2×10 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was chromatographed on a silica gel column with ethyl acetate/petroleum ether (1/2) to yield 0.600 g (58% yield) of tert-butyl 4-[[2-fluoro-4-(2-methylpyridin-4-yl)phenyl]methyl]piperazine-1-carboxylate as yellow oil. LCMS (ESI, m/z): 386 [M+H]+.

Workup

  1. customA 25 mL round-bottom flask was purged with and
  2. temperaturemaintained under an inert atmosphere of nitrogen
  3. customThe reaction was then quenched by the addition of water (10 mL)
  4. extractionThe resulting solution was extracted with ethyl acetate (3×10 mL)
  5. washwashed with brine (2×10 mL)
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was chromatographed on a silica gel column with ethyl acetate/petroleum ether (1/2)

Sources & evidence

ORD record
ord-faedac8e2a0948daaba0f208142347dd
Source dataset
uspto-grants-2015_09
Patent number
US09133148B2

Reaction notes

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