Water → HCID 86721870, compound

HRID 1049013Notes

Reaction equation

HRID 1049013 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([OH:14])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[CH:17]1([N:21]([C:32]2[CH:37]=[CH:36][CH:35]=[C:34]([F:38])[CH:33]=2)[S:22]([C:25]2[CH:30]=[CH:29][C:28](F)=[CH:27][CH:26]=2)(=[O:24])=[O:23])[CH2:20][CH2:19][CH2:18]1.O>C1COCC1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:28]2[CH:29]=[CH:30][C:25]([S:22](=[O:23])(=[O:24])[N:21]([CH:17]3[CH2:18][CH2:19][CH2:20]3)[C:32]3[CH:37]=[CH:36][CH:35]=[C:34]([F:38])[CH:33]=3)=[CH:26][CH:27]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylateHCID 86721869HCID 86721869, compound

Product 1

HCID 86721870HCID 86721870, compoundYield 105.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of tert-butyl-4-hydroxy-1-piperidinecarboxylate (137 mg, 681 mmol) in anhydrous THF (5 mL) was added NaH (60% dispersion in mineral oil, 30 mg, 743 mmol) and the reaction was stirred at room temperature for 15 minutes. N-Cyclobutyl-4-fluoro-N-(3-fluoro-phenyl)-benzenesulfonamide (200 mg, 619 μmol) was added and the reaction was heated at 90° C. for 4 hours. The reaction was left to cool to room temperature, water added and extracted with EtOAc, washed with brine, dried with Na2SO4 then concentrated and purified by silica gel column chromatography (0-50% EtOAc in cyclohexane) to give 4-{4-[cyclobutyl-(3-fluoro-phenyl)-sulfamoyl]-phenoxy}-piperidine-1-carboxylic acid tert-butyl ester (330 mg). LCMS (m/z, Method A) ES+ 527 [M+23]+.

Workup

  1. temperaturethe reaction was heated at 90° C. for 4 hours
  2. waitThe reaction was left
  3. temperatureto cool to room temperature
  4. extractionextracted with EtOAc
  5. washwashed with brine
  6. dry with materialdried with Na2SO4
  7. concentrationthen concentrated
  8. custompurified by silica gel column chromatography (0-50% EtOAc in cyclohexane)

Sources & evidence

ORD record
ord-3fa5f8c43f054241b2d03bceb4395ec1
Source dataset
uspto-grants-2016_07
Patent number
US09382222B2

Reaction notes

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