Sodium Hydroxide → HCID 23149806, compound

HRID 1670759Notes

Reaction equation

HRID 1670759 reaction equation
Br[C:2]1[CH:3]=[C:4]([F:12])[CH:5]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=1.CCCCCC.C([Li])CCC.C(OC([N:31]1[CH2:36][CH2:35][C:34](=[O:37])[CH2:33][CH2:32]1)=O)(C)(C)C.[OH-].[Na+]>C(OCC)C.O>[F:12][C:4]1[CH:3]=[C:2]([C:34]2([OH:37])[CH2:35][CH2:36][NH:31][CH2:32][CH2:33]2)[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=1

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 27363233-Bromo-5-fluorobenzotrifluorideHCID 178418244HCID 178418244, compound

Product 1

HCID 23149806HCID 23149806, compoundYield 111.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 3283Diethyl EtherSolvent

Conditions

Temperature
-78 °C

Procedure

5-Bromo-3-fluorobenzo trifluoride (APOLLO Co., 9.0 g) was dissolved in diethyl ether (110 ml), and the mixture was cooled to −78° C. An n-butyllithium hexane solution (2.71 M, 17.5 ml) was added to this solution, and the mixture was stirred at −78° C. for 1 hr. Then, 1-(tert-butoxycarbonyl)-4-piperidone (6.71 g) was added. The reaction temperature was then warmed to 0° C., and the mixture was further stirred for 1 hr. After completion of the reaction, water was added, and the mixture was extracted three times with ethyl acetate. The organic layer was dried and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (elution solvent: hexane-ethyl acetate (5:1-2:1)). Then, the residue was dissolved in 1,4-dioxane (150 ml), and 10% aqueous sulfuric acid (10 ml) was added thereto. The mixture was stirred with heating at 70° C. for 2 hr. After completion of the reaction, the reaction system was basified (pH=9) with an 1N aqueous sodium hydroxide solution, and extracted three times with chloroform. The organic layer was dried and the solvent was evaporated under reduced pressure to give 4-[3-fluoro-5-(trifluoromethyl)phenyl]piperidin-4-ol (9.89 g, yield 56%).

Workup

  1. temperatureThe reaction temperature was then warmed to 0° C.
  2. stirringthe mixture was further stirred for 1 hr
  3. additionwas added
  4. extractionthe mixture was extracted three times with ethyl acetate
  5. customThe organic layer was dried
  6. customthe solvent was evaporated under reduced pressure
  7. customThe obtained residue was purified by silica gel column chromatography (elution solvent: hexane-ethyl acetate (5:1-2:1))
  8. dissolutionThen, the residue was dissolved in 1,4-dioxane (150 ml)
  9. addition10% aqueous sulfuric acid (10 ml) was added
  10. stirringThe mixture was stirred
  11. temperaturewith heating at 70° C. for 2 hr
  12. customAfter completion of the reaction
  13. extractionextracted three times with chloroform
  14. customThe organic layer was dried
  15. customthe solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-bae5c528bfac49e7ac698f8772a0e827
Source dataset
uspto-grants-2011_08
Patent number
US07994196B2

Reaction notes

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