Hexane → 2-Chloro-3-[1-(4-chlorophenylsulfonyl)cyclohexyl]pyridine

HRID 748722Notes

Reaction equation

HRID 748722 reaction equation
C([Li])CCC.[CH3:6][CH2:7][CH2:8][CH2:9][CH2:10]C.[Cl:12][C:13]1[C:18]([CH2:19][S:20]([C:23]2[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][CH:24]=2)(=[O:22])=[O:21])=[CH:17][CH:16]=[CH:15][N:14]=1.ICCCCCI>O.C(COC)OC>[Cl:12][C:13]1[C:18]([C:19]2([S:20]([C:23]3[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][CH:24]=3)(=[O:22])=[O:21])[CH2:10][CH2:9][CH2:8][CH2:7][CH2:6]2)=[CH:17][CH:16]=[CH:15][N:14]=1

Participants

7

Reactant 4

HCID 8058HexaneHCID 123541,5-DiiodopentaneHCID 230286692-Chloro-3-(4-chlorophenylsulfonylmethyl)pyridineHCID 178418339Butyllithium

Product 1

HCID 597509272-Chloro-3-[1-(4-chlorophenylsulfonyl)cyclohexyl]pyridineYield 38%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
-78 °C

Procedure

At −78° C., butyl lithium (a 1.57M hexane solution; 0.66 ml, 1.03 mmol) was added dropwise to a dimethoxyethane (5 ml) solution of the 2-chloro-3-(4-chlorophenylsulfonylmethyl)pyridine (156 mg, 0.516 mmol) obtained in Example 98. At −78° C., the resulting mixture was stirred for 20 minutes, followed by the addition of 1,5-diiodopentane (0.092 ml, 0.619 mmol). The temperature of the reaction mixture was gradually elevated to room temperature, at which stirring was performed for 15 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 15% ethyl acetate/hexane 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 (72 mg, 38%) as a white solid. The resulting solid was washed with hexane-ether and then collected by filtration, whereby the title compound was obtained as a white powder.

Workup

  1. customAt −78° C.
  2. customwas gradually elevated to room temperature, at which
  3. stirringstirring
  4. waitwas performed for 15 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 15% ethyl acetate/hexane eluate
  11. concentrationwas concentrated under reduced pressure
  12. customThe residue thus obtained
  13. customwas purified by high performance liquid chromatography (

Sources & evidence

ORD record
ord-9b839f7882224ddb80414fb3848caab4
Source dataset
uspto-grants-2008_07
Patent number
US07399775B2

Reaction notes

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