Hydrochloric Acid → 2-(4-Octyloxyphenyl)-5-hydroxy-6-fluoropyridine

HRID 1780548Notes

Reaction equation

HRID 1780548 reaction equation
C([N-]C(C)C)(C)C.[Li+].[F:9][C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([C:16]2[CH:21]=[CH:20][C:19]([O:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH3:30])=[CH:18][CH:17]=2)[N:11]=1.B(OC(C)C)(OC(C)C)[O:32]C(C)C.Cl.[Cl-].[Na+]>O1CCCC1.CCCCCC.C(C1C=CC=CC=1)C.O1CCCC1>[F:9][C:10]1[C:15]([OH:32])=[CH:14][CH:13]=[C:12]([C:16]2[CH:21]=[CH:20][C:19]([O:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH3:30])=[CH:18][CH:17]=2)[N:11]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 5234Sodium ChlorideHCID 21531Triisopropyl borateHCID 2724682Lithium diisopropylamideHCID 179115002-(4-Octyloxyphenyl)-6-fluoropyridine

Product 1

HCID 190469612-(4-Octyloxyphenyl)-5-hydroxy-6-fluoropyridineYield 45.6%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 86585711HCID 86585711, compoundSolvent

Procedure

4.3 ml (8.6 mmol) of a 2-molar lithium diisopropylamide solution in tetrahydrofuran/hexane/ethylbenzene are added dropwise at -78° C. to 2.36 g (7.8 mmol) of 2-fluoro-6-(4-octyloxyphenyl)pyridine (prepared as described in Example 2) in 180 ml of tetrahydrofuran, and the mixture is stirred for 4 hours. 2.95 g (17.2 mmol) of triisopropyl borate in 10 ml of tetrahydrofuran are then added dropwise at -78° C., and the reaction mixture is stirred overnight, during which it warms to room temperature. After addition of 12.0 ml of 10% hydrochloric acid and stirring at room temperature for i 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. The residue is taken up in 40 ml of ether, and the resulting mixture is heated to boiling. 8.03 g (23.5 mmol) of a 10% hydrogen peroxide solution are added dropwise, and the reaction mixture is refluxed for 4 hours. After separating off the ether phase, the aqueous phase is extracted with ether. The combined ether phases are washed with sodium sulfite solution and then with sodium chloride solution, dried over sodium sulfate, filtered and evaporated to dryness. Purification of the residue by chromatography (silica gel, 7:3 hexane/ethyl acetate) gives 1.13 g of 2-fluoro-3-hydroxy-6-(4-octyloxyphenyl)pyridine. ##STR18##

Workup

  1. stirringthe reaction mixture is stirred overnight, during which it
  2. customwarms to room temperature
  3. additionis added
  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. temperaturethe resulting mixture is heated to boiling
  10. addition8.03 g (23.5 mmol) of a 10% hydrogen peroxide solution are added dropwise
  11. temperaturethe reaction mixture is refluxed for 4 hours
  12. customAfter separating off the ether phase
  13. extractionthe aqueous phase is extracted with ether
  14. washThe combined ether phases are washed with sodium sulfite solution
  15. dry with materialwith sodium chloride solution, dried over sodium sulfate
  16. filtrationfiltered
  17. customevaporated to dryness
  18. customPurification of the residue by chromatography (silica gel, 7:3 hexane/ethyl acetate)

Sources & evidence

ORD record
ord-3d827680a6c2499d89b7aca5d6e5c3a1
Source dataset
uspto-grants-1997_05
Patent number
US05630962

Reaction notes

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