Trifluoroacetic acid → 4-[4-Fluoro-3-(trifluoromethyl)phenyl]piperidin-4-ol

HRID 2105948Notes

Reaction equation

HRID 2105948 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([OH:21])[CH2:13][CH2:12][N:11](C(OC(C)(C)C)=O)[CH2:10][CH2:9]2)=[CH:4][C:3]=1[C:22]([F:25])([F:24])[F:23].FC(F)(F)C(O)=O.[OH-].[Na+]>C(Cl)Cl>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([OH:21])[CH2:9][CH2:10][NH:11][CH2:12][CH2:13]2)=[CH:4][C:3]=1[C:22]([F:25])([F:23])[F:24]

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 14798Sodium HydroxideHCID 68622938HCID 68622938, compound

Product 1

HCID 231499084-[4-Fluoro-3-(trifluoromethyl)phenyl]piperidin-4-olYield 41.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl 4-[4-fluoro-3-(trifluoro-methyl)phenyl]-4-hydroxypiperidine-1-carboxylate (4.25 g, 11.7 mmol) in methylen chloride (30 ml) was added trifluoroacetic acid (4 ml) and the solution was stirred at ambient temperature for 20 h. 1 M aqueous sodium hydroxide (50 ml) was added and the aqueous phase was extracted with methylen chloride (3×50 ml). The combined organic phases was dried (MgSO4), filtered and evaporated to dryness. The residue was purified by flash column chromatography (ethylacetate/methanol, 1:1) to give the title compound (1.28 g). MS m/z (rel. intensity, 70 eV) 263 (M+, 9), 245 (59), 244 (29), 163 (20), 56 (bp).

Workup

  1. extractionthe aqueous phase was extracted with methylen chloride (3×50 ml)
  2. dry with materialThe combined organic phases was dried (MgSO4)
  3. filtrationfiltered
  4. customevaporated to dryness
  5. customThe residue was purified by flash column chromatography (ethylacetate/methanol, 1:1)

Sources & evidence

ORD record
ord-9e2e2354fe9b4546be0db350b2dc4a58
Source dataset
uspto-grants-2009_08
Patent number
US07579474B2

Reaction notes

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