1-Bromo-2-Chloroethane → 4-[4-Benzenesulfonyl-2-(2-chloro-ethoxy)-phenylamino]-piperidine-1-carboxylic acid tert-butyl ester

HRID 2224077Notes

Reaction equation

HRID 2224077 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([NH:14][C:15]2[CH:20]=[CH:19][C:18]([S:21]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)(=[O:23])=[O:22])=[CH:17][C:16]=2[OH:30])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])[O-].[K+].[K+].Br[CH2:38][CH2:39][Cl:40]>C(#N)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([NH:14][C:15]2[CH:20]=[CH:19][C:18]([S:21]([C:24]3[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=3)(=[O:23])=[O:22])=[CH:17][C:16]=2[O:30][CH2:38][CH2:39][Cl:40])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 78491-Bromo-2-Chloroethane2×HCID 11430Potassium CarbonateHCID 684357554-(4-Benzenesulfonyl-2-hydroxy-phenylamino)-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 684332104-[4-Benzenesulfonyl-2-(2-chloro-ethoxy)-phenylamino]-piperidine-1-carboxylic acid tert-butyl esterYield 80%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of 4-(4-benzenesulfonyl-2-hydroxy-phenylamino)-piperidine-1-carboxylic acid tert-butyl ester (0.192 g., 0.444 mmol) in 1 mL acetonitrile is added potassium carbonate (0.245 g., 1.776 mmol) and then 1-bromo-2-chloro-ethane (0.044 mL, 0.535 mmol) dropwise. The suspension is refluxed under nitrogen for 3 hours, at which time is added 1-bromo-2-chloro-ethane (0.044 mL, 0.535 mmol) dropwise. Reflux is continued for another 1.5 hours. The reaction mixture is concentrated in vacuo and the resulting oil is dissolved in 75 mL ethyl acetate, washed with 2×50 mL water and 50 mL brine, then dried over sodium sulfate and concentrated in vacuo. The resulting crude oil is purified by flash chromatography (10% -30% ethyl acetate in hexanes) to give 0.175 g (0.35 mmol, 80%) of 4-[4-benzenesulfonyl-2-(2-chloro-ethoxy)-phenylamino]-piperidine-1-carboxylic acid tert-butyl ester as a clear oil. MS: 439 (M−tBu+H)+.

Workup

  1. temperatureThe suspension is refluxed under nitrogen for 3 hours, at which time
  2. temperatureReflux
  3. concentrationThe reaction mixture is concentrated in vacuo
  4. dissolutionthe resulting oil is dissolved in 75 mL ethyl acetate
  5. washwashed with 2×50 mL water and 50 mL brine
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated in vacuo
  8. customThe resulting crude oil is purified by flash chromatography (10% -30% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-62599da5fe9a4d7fb0c864ab50435c43
Source dataset
uspto-grants-2008_05
Patent number
US07378415B2

Reaction notes

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