Hexane → 4-Chloro-3-[1-(4-chlorophenylsulfonyl)cyclohexyl]pyridine

HRID 748723Notes

Reaction equation

HRID 748723 reaction equation
C([Li])CCC.[CH3:6][CH2:7][CH2:8][CH2:9][CH2:10]C.[Cl:12][C:13]1[CH:18]=[CH:17][N:16]=[CH:15][C:14]=1[CH2:19][S:20]([C:23]1[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][CH:24]=1)(=[O:22])=[O:21].ICCCCCI>O.C(COC)OC>[Cl:12][C:13]1[CH:18]=[CH:17][N:16]=[CH:15][C:14]=1[C:19]1([S:20]([C:23]2[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][CH:24]=2)(=[O:21])=[O:22])[CH2:10][CH2:9][CH2:8][CH2:7][CH2:6]1

Participants

7

Reactant 4

HCID 8058HexaneHCID 123541,5-DiiodopentaneHCID 230288934-Chloro-3-(4-chlorophenylsulfonylmethyl)pyridineHCID 178418339Butyllithium

Product 1

HCID 597508974-Chloro-3-[1-(4-chlorophenylsulfonyl)cyclohexyl]pyridineYield 18%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
-78 °C

Procedure

At −78° C., butyl lithium (a 1.57M hexane solution; 0.58 ml, 0.913 mmol) was added dropwise to a dimethoxyethane (5 ml) solution of the 4-chloro-3-(4-chlorophenylsulfonylmethyl)pyridine (138 mg, 0.457 mmol) obtained in Example 104. At −78° C., the resulting mixture was stirred for 20 minutes and then 1,5-diiodopentane (0.068 ml, 0.457 mmol) was added thereto. The temperature of the reaction mixture was gradually raised to room temperature, at which stirring was performed for 17 hours. Water was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with brine and then dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The residue was subjected to flash chromatography on a silica gel column, and the fraction obtained from the hexane:ethyl acetate (=2:1) eluate was concentrated under reduced pressure. The residue thus obtained was purified by high performance liquid chromatography (using a mixed solvent of water/acetonitrile/formic acid) to give the title compound (30 mg, 18%) as a white solid. The resulting solid was washed with ether and then collected by filtration, whereby the title compound was obtained as a white powder.

Workup

  1. customAt −78° C.
  2. temperatureThe temperature of the reaction mixture was gradually raised to room temperature, at which
  3. stirringstirring
  4. waitwas performed for 17 hours
  5. extractionfollowed by extraction with ethyl acetate
  6. washThe organic layer was washed with brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationAfter filtration
  9. concentrationthe filtrate was concentrated under reduced pressure
  10. customthe fraction obtained from the hexane
  11. concentrationethyl acetate (=2:1) eluate was concentrated under reduced pressure
  12. customThe residue thus obtained
  13. customwas purified by high performance liquid chromatography (

Sources & evidence

ORD record
ord-682456acca894cd5b39a66908ec923be
Source dataset
uspto-grants-2008_07
Patent number
US07399775B2

Reaction notes

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