Water → HCID 67991724, compound

HRID 1777380Notes

Reaction equation

HRID 1777380 reaction equation
[O:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[N:7]1[C:11](B2OC(C)(C)C(C)(C)O2)=[CH:10][CH:9]=[N:8]1.Br[C:22]1[CH:27]=[CH:26][C:25]([F:28])=[CH:24][N:23]=1.C([O-])([O-])=O.[Na+].[Na+].O>C(O)C.C1(C)C=CC=CC=1.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.CCOC(C)=O>[F:28][C:25]1[CH:26]=[CH:27][C:22]([C:11]2[N:7]([CH:2]3[CH2:3][CH2:4][CH2:5][CH2:6][O:1]3)[N:8]=[CH:9][CH:10]=2)=[N:23][CH:24]=1

Participants

9

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 27831712-Bromo-5-fluoropyridineHCID 115872081-(tetrahydro-2H-pyran-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole

Product 1

HCID 67991724HCID 67991724, compoundYield 122.6%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a mixed solution of 1-(tetrahydro-2H-pyran-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (100.5 g, 0.36 mol), 2-bromo-5-fluoropyridine (56.5 g, 0.33 mol), and Pd(PPh3)4 (38.0 g, 32.6 mmol) in ethanol (300 mL) and toluene (300 mL), a 2M aqueous solution of Na2CO3 (0.49 L, 0.99 mol) was added, and the resulting mixture was heated to reflux for 2 hours. The reaction mixture was allowed to cool to room temperature, then water and EtOAc were added thereto, and the resulting mixture was stirred at room temperature for 30 minutes, followed by extraction with EtOAc. The organic layer was washed with a saturated aqueous solution of sodium chloride, dried over MgSO4, then the drying agent was filtered off, then NH silica gel (400 g) was added thereto, and the resulting mixture was stirred for 15 hours. The mixture was filtered through acid silica gel (eluted with n-hexane:AcOEt=1:1→AcOEt) and the solvent was distilled off under reduced pressure to obtain the title compound (100 g) (pale yellow oil).

Workup

  1. temperaturethe resulting mixture was heated
  2. temperatureto reflux for 2 hours
  3. extractionfollowed by extraction with EtOAc
  4. washThe organic layer was washed with a saturated aqueous solution of sodium chloride
  5. dry with materialdried over MgSO4
  6. filtrationthe drying agent was filtered off
  7. additionNH silica gel (400 g) was added
  8. stirringthe resulting mixture was stirred for 15 hours
  9. filtrationThe mixture was filtered through acid silica gel (eluted with n-hexane:AcOEt=1:1→AcOEt)
  10. distillationthe solvent was distilled off under reduced pressure

Sources & evidence

ORD record
ord-c61782bb9f3b41b29052b21475f3e144
Source dataset
uspto-grants-2016_02
Patent number
US09266870B2

Reaction notes

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