Potassium Carbonate → HCID 67367623, compound

HRID 1752023Notes

Reaction equation

HRID 1752023 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[CH2:20][O:21]S(C)(=O)=O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C([O-])([O-])=O.[K+].[K+].[F:32][C:33]1[CH:38]=[C:37]([F:39])[CH:36]=[C:35]([F:40])[C:34]=1O>CC#N>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[CH2:20][O:21][C:34]2[C:33]([F:32])=[CH:38][C:37]([F:39])=[CH:36][C:35]=2[F:40])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 5199742,4,6-TrifluorophenolHCID 462130464-(2-Methanesulfonyloxymethylphenyl)piperidine-1-carboxylic Acid t-Butyl Ester

Product 1

HCID 67367623HCID 67367623, compoundYield 86.1%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
50 °C

Procedure

4-(2-Methanesulfonyloxymethylphenyl)piperidine-1-carboxylic acid t-butyl ester (27.0 g, 60.6 mmol, 1.0 eq.) was dissolved in MeCN (540 mL) and added to K2CO3 (25 g, 180 mmol, 3.0 eq.) and 2,4,6-trifluorophenol (13.5 g, 90.9 mmol, 1.5 eq.). The mixture was vigorously stirred at 50° C. for 6 hours, removed from the heat, and stirred overnight. The mixture was cooled at room temperature, and diluted with EtOAc (700 mL) and water (700 mL). The phases were separated, and the organic layer was washed twice with 1.0 M NaOH in water (2×400 mL) and saturated aqueous NaCl (1×400 mL), then dried over Na2SO4 and the solvent removed to yield crude 4-[2-(2,4,6-trifluorophenoxymethyl)-phenyl]piperidine-1-carboxylic acid t-butyl ester (25.0 g). The crude product was combined with smaller scale runs for a total of 30 g, and purified by chromatography (0-10% EtOAc in hexanes) to yield 4-[2-(2,4,6-trifluorophenoxymethyl)phenyl]piperidine-1-carboxylic acid t-butyl ester (22.0 g).

Workup

  1. customremoved from the heat
  2. stirringstirred overnight
  3. temperatureThe mixture was cooled at room temperature
  4. additiondiluted with EtOAc (700 mL) and water (700 mL)
  5. customThe phases were separated
  6. washthe organic layer was washed twice with 1.0 M NaOH in water (2×400 mL) and saturated aqueous NaCl (1×400 mL)
  7. dry with materialdried over Na2SO4
  8. customthe solvent removed
  9. customto yield crude 4-[2-(2,4,6-trifluorophenoxymethyl)-phenyl]piperidine-1-carboxylic acid t-butyl ester (25.0 g)
  10. custompurified by chromatography (0-10% EtOAc in hexanes)

Sources & evidence

ORD record
ord-4259a3fbd2294919bbe6687c53a8187f
Source dataset
uspto-grants-2015_10
Patent number
US09162982B2

Reaction notes

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