Cesium carbonate → 1-tert-Butoxycarbonyl-4-[(4-hydroxyphenyl)sulfanyl]piperidine

HRID 2074229Notes

Reaction equation

HRID 2074229 reaction equation
CS(Cl)(=O)=O.O[CH:7]1[CH2:12][CH2:11][N:10]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:9][CH2:8]1.C(=O)([O-])[O-].[Cs+].[Cs+].[SH:26][C:27]1[CH:32]=[CH:31][C:30]([OH:33])=[CH:29][CH:28]=1>CC(N(C)C)=O.O.CCOC(C)=O.C1COCC1>[OH:33][C:30]1[CH:31]=[CH:32][C:27]([S:26][CH:7]2[CH2:12][CH2:11][N:10]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:9][CH2:8]2)=[CH:28][CH:29]=1

Participants

9

Reactant 4

HCID 10796Cesium carbonateHCID 31297Methanesulfonyl chlorideHCID 2401474-MercaptophenolHCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylate

Product 1

HCID 185387571-tert-Butoxycarbonyl-4-[(4-hydroxyphenyl)sulfanyl]piperidineYield 73.4%

Reagents, catalysts & solvents 4

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 31374DimethylacetamideSolvent

Procedure

TEA (2.30 ml) and methanesulfonyl chloride (1.22 ml) were dropwise added to a THF (40 ml) solution containing tert-butyl 4-hydroxypiperidine-1-carboxylate (3.02 g) at 0° C., followed by stirring at room temperature for 1 hour. EtOAc (50 ml) and water (50 ml) were added to the reaction solution. The organic layer was washed with aqueous 5% citric acid solution, an aqueous saturated sodium hydrogencarbonate solution and saturated brine in that order, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure to obtain a pale orange oil. The resulting oil was dissolved in DMA (25 ml), and cesium carbonate (5.38 g) and 4-sulfanylphenol (1.89 g) were added thereto, followed by heating at 50° C. for 2 hours. The reaction solution was cooled, water was added thereto, followed by extraction with EtOAc. The organic layer was washed with an aqueous 1 M hydrochloric acid solution and saturated brine in that order, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (eluent: hexane:EtOAc=4:1 (v/v)) to obtain tert-butyl 4-[(4-hydroxyphenyl)sulfanyl]piperidine-1-carboxylate (3.40 g) as colorless powder.

Workup

  1. washThe organic layer was washed with aqueous 5% citric acid solution
  2. dry with materialan aqueous saturated sodium hydrogencarbonate solution and saturated brine in that order, and dried over anhydrous sodium sulfate
  3. customThe solvent was evaporated under reduced pressure
  4. customto obtain a pale orange oil
  5. temperatureby heating at 50° C. for 2 hours
  6. temperatureThe reaction solution was cooled
  7. extractionfollowed by extraction with EtOAc
  8. washThe organic layer was washed with an aqueous 1 M hydrochloric acid solution and saturated brine in that order
  9. dry with materialdried over anhydrous sodium sulfate
  10. customThe solvent was evaporated under reduced pressure
  11. customthe residue was purified by silica gel column chromatography (eluent: hexane:EtOAc=4:1 (v/v))

Sources & evidence

ORD record
ord-2d7f6b552a974f1e82e514862660b020
Source dataset
uspto-grants-2011_04
Patent number
US07919494B2

Reaction notes

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