Hydrochloric Acid → 2-Fluoro-6-(4-octyloxyphenyl)pyridine-3-boronic acid

HRID 1780557Notes

Reaction equation

HRID 1780557 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[F:13][C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([C:20]2[CH:25]=[CH:24][C:23]([O:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH3:34])=[CH:22][CH:21]=2)[N:15]=1.[B:35](OC(C)C)([O:40]C(C)C)[O:36]C(C)C.Cl.[Cl-].[Na+]>O1CCCC1.CCCCCC>[F:13][C:14]1[C:19]([B:35]([OH:40])[OH:36])=[CH:18][CH:17]=[C:16]([C:20]2[CH:25]=[CH:24][C:23]([O:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH3:34])=[CH:22][CH:21]=2)[N:15]=1

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 5234Sodium ChlorideHCID 7912DiisopropylamineHCID 21531Triisopropyl borateHCID 179115002-(4-Octyloxyphenyl)-6-fluoropyridineHCID 178418339Butyllithium

Product 1

HCID 190469502-Fluoro-6-(4-octyloxyphenyl)pyridine-3-boronic acidYield 78.5%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Conditions

Temperature
-78 °C

Procedure

8.00 ml (56.80 mmol) of diisopropylamine in 10 ml of tetrahydrofuran are stirred at 0° C. with 35.70 ml (56.80 mmol) of a 1.6-molar n-butyllithium solution in hexane for 1 hour. After cooling to -78° C., 8.56 g (28.40 mmol) of 2-fluoro-6-(4-octyloxyphenyl)pyridine (prepared as described in Example 2) in 1000 ml of tetrahydrofuran are added dropwise, and the mixture is stirred at -78° C. for 4 hours. 21.25 g (113.00 mmol) of triisopropyl borate are then added dropwise at -78° C., and the reaction mixture is stirred overnight, during which it warms to room temperature. After addition of 100 ml of 10% hydrochloric acid and stirring at room temperature for one hour, sodium chloride solution is added, the mixture is extracted with ether, the ether phase is washed with sodium chloride solution, dried over sodium sulfate, filtered and concentrated. Recrystallization from acetonitrile gives 7.70 g of 2-fluoro-6-(4-octyloxyphenyl)pyridine-3-boronic acid. ##STR29##

Workup

  1. stirringthe reaction mixture is stirred overnight, during which it
  2. customwarms to room temperature
  3. stirringstirring at room temperature for one hour
  4. extractionthe mixture is extracted with ether
  5. washthe ether phase is washed with sodium chloride solution
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customRecrystallization from acetonitrile

Sources & evidence

ORD record
ord-4962c978bc824e2e99e63ceab2130d15
Source dataset
uspto-grants-1997_05
Patent number
US05630962

Reaction notes

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