Triisopropyl borate → HCID 19387549, compound

HRID 1757355Notes

Reaction equation

HRID 1757355 reaction equation
C([Li])CCC.Br[C:7]1[CH:8]=[C:9]([F:28])[C:10]([C:13]2[CH:18]=[CH:17][C:16]([O:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH3:27])=[CH:15][CH:14]=2)=[N:11][CH:12]=1.B(OC(C)C)(OC(C)C)[O:30]C(C)C.[Cl-].[NH4+]>CCCCCC.O1CCCC1.CCOCC>[F:28][C:9]1[C:10]([C:13]2[CH:18]=[CH:17][C:16]([O:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH3:27])=[CH:15][CH:14]=2)=[N:11][CH:12]=[C:7]([OH:30])[CH:8]=1

Participants

8

Reactant 4

HCID 21531Triisopropyl borateHCID 25517Ammonium ChlorideHCID 193875465-Bromo-3-fluoro-2-(4-octyloxyphenyl)pyridineHCID 178418339Butyllithium

Product 1

HCID 19387549HCID 19387549, compoundYield 80%

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent

Conditions

Temperature
-70 °C

Procedure

15 ml (24.00 mmol) of 1.6 molar n-butyllithium solution in hexane are added dropwise to a solution, cooled to -70° C., of 7.61 g (20.00 mmol) of 5-bromo-3-fluoro-2-(4-octyloxyphenyl)pyridine in 400 ml of tetrahydrofuran, and the mixture is stirred at -70° C. for 15 minutes. 7.5 g (40.00 mmol) of triisopropyl borate are subsequently added dropwise, the mixture is stirred at -70° C. for 1.5 hours and warmed to room temperature, 500 ml of ammonium chloride solution and 500 ml of ether are added, and the organic phase is separated off and washed twice with aqueous sodium chloride solution, dried over sodium sulfate and evaporated. The resultant 3-fluoro-2-(4-octyloxyphenyl)pyridine-5-boronic acid is refluxed for 2 hours in 100 ml of tetrahydrofuran with 30 ml of 17.5% strength by weight aqueous hydrogen peroxide solution and subsequently cooled to 0° C., and 200 ml of aqueous sodium sulfite solution are added dropwise. The organic phase is separated off, washed twice with aqueous sodium chloride solution, dried over sodium sulfate and evaporated to dryness. Recrystallization from 1,2-dichloroethane gives 5.08 g of 3-fluoro-5-hydroxy-2-(4-octyloxyphenyl)pyridine. ##STR17##

Workup

  1. stirringthe mixture is stirred at -70° C. for 1.5 hours
  2. temperaturewarmed to room temperature
  3. customthe organic phase is separated off
  4. washwashed twice with aqueous sodium chloride solution
  5. dry with materialdried over sodium sulfate
  6. customevaporated
  7. temperatureThe resultant 3-fluoro-2-(4-octyloxyphenyl)pyridine-5-boronic acid is refluxed for 2 hours in 100 ml of tetrahydrofuran with 30 ml of 17.5% strength by weight aqueous hydrogen peroxide solution
  8. temperaturesubsequently cooled to 0° C.
  9. addition200 ml of aqueous sodium sulfite solution are added dropwise
  10. customThe organic phase is separated off
  11. washwashed twice with aqueous sodium chloride solution
  12. dry with materialdried over sodium sulfate
  13. customevaporated to dryness
  14. customRecrystallization from 1,2-dichloroethane

Sources & evidence

ORD record
ord-2252d51b9911469f9906d1f3af16f3d4
Source dataset
uspto-grants-1995_08
Patent number
US05445763

Reaction notes

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