Potassium Carbonate → 4-[4-(4-Fluoro-benzenesulfonyl)-phenylamino]-piperidine-1-carboxylic acid tert-butyl ester

HRID 511087Notes

Reaction equation

HRID 511087 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([NH2:14])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].F[C:16]1[CH:21]=[CH:20][C:19]([S:22]([C:25]2[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=2)(=[O:24])=[O:23])=[CH:18][CH:17]=1.C(=O)([O-])[O-].[K+].[K+]>CS(C)=O.ClCCl>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([NH:14][C:16]2[CH:17]=[CH:18][C:19]([S:22]([C:25]3[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=3)(=[O:24])=[O:23])=[CH:20][CH:21]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 67842Benzene, 1,1'-sulfonylbis(4-fluoro-HCID 12682914-Amino-1-Boc-piperidine

Product 1

HCID 585762724-[4-(4-Fluoro-benzenesulfonyl)-phenylamino]-piperidine-1-carboxylic acid tert-butyl esterYield 77.3%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
120 °C

Procedure

A solution of 4-amino-piperidine-1-carboxylic acid tert-butyl ester (427 mg; 2.13 mmol), bis(4-fluorophenyl) sulfone (493 mg; 1.94 mmol) and potassium carbonate (1.01 g; 7.76 mmol) in dimethylsulfoxide (5 mL) is heated over night at 100° C. The temperature is then increased to 120° C. and the mixture is reacted at this temperature for 24 hours. The reaction is then diluted with dichloromethane (100 mL), filtered and the filtrate is washed with aq. 1N hydrochloric acid (2×20 mL), and water (2×20 mL). The organic layer is dried over magnesium sulfate, filtered and concentrated under reduced pressure. The residue obtained is finally purified by column chromatography on silica gel (dichloromethane:methanol 100:0 (200 mL) and then 98:2 (150 mL)) to afford the desired product (653 mg; 1.50 mmol).

Workup

  1. customthe mixture is reacted at this temperature for 24 hours
  2. filtrationfiltered
  3. washthe filtrate is washed with aq. 1N hydrochloric acid (2×20 mL), and water (2×20 mL)
  4. dry with materialThe organic layer is dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue obtained
  8. customis finally purified by column chromatography on silica gel (dichloromethane:methanol 100:0 (200 mL)

Sources & evidence

ORD record
ord-369605a0468a47429ba5d662e95592a9
Source dataset
uspto-grants-2015_08
Patent number
US09096524B2

Reaction notes

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