Pyridine → 4-Phenylbicyclo[2.2.2]oct-1-ylmethyl toluene-4-sulfonate

HRID 908127Notes

Reaction equation

HRID 908127 reaction equation
N1C=CC=CC=1.[C:7]1([CH3:17])[CH:12]=[CH:11][C:10]([S:13](Cl)(=[O:15])=[O:14])=[CH:9][CH:8]=1.[C:18]1([C:24]23[CH2:31][CH2:30][C:27]([CH2:32][OH:33])([CH2:28][CH2:29]2)[CH2:26][CH2:25]3)[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>C(Cl)Cl.CN(C)C1C=CN=CC=1>[C:7]1([CH3:17])[CH:12]=[CH:11][C:10]([S:13]([O:33][CH2:32][C:27]23[CH2:26][CH2:25][C:24]([C:18]4[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=4)([CH2:29][CH2:28]2)[CH2:31][CH2:30]3)(=[O:15])=[O:14])=[CH:9][CH:8]=1

Participants

6

Reactant 3

HCID 1049Pyridine2×HCID 73974-Toluenesulfonyl chloride2×HCID 21675352(4-Phenylbicyclo[2.2.2]oct-1-yl)methanol

Product 1

HCID 866252464-Phenylbicyclo[2.2.2]oct-1-ylmethyl toluene-4-sulfonateYield 89.2%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent4×

Conditions

Temperature
2.5 °C

Procedure

Pyridine (4 mL), then a solution of toluene-4-sulfonyl chloride (7.4 g, 38.81 mmol) in dry DCM (30 mL), were added to a stirred solution of (4-phenylbicyclo[2.2.2]oct-1-yl)methanol (7.0 g, 32.36 mmol) in DCM (70 mL), maintaining 0-5° C. throughout. The reaction mixture was stirred at 0° C. overnight, refluxed for 2 h then cooled to 35° C. Further pyridine (2 mL) and a solution of toluene-4-sulfonyl chloride (3.9 g) in DCM (10 mL) were added and the mixture stirred at reflux for 2 h. As some starting material remained, a catalytic amount of 4-dimethylaminopyridine was added and the mixture stirred under reflux overnight. The mixture was cooled, diluted with DCM (200 mL) then washed with water (100 mL), hydrochloric acid (2M; 150 mL), water (50 mL), sat. aq. NaHCO3 (100 mL), water (50 mL) and brine (50 mL). After drying (MgSO4) the solution was concentrated to give crude product which was purified by silica column chromatography (silica 40-63 micron) eluting with hexane:ethyl acetate (19:1 to 4:1) to afford the title compound as a pale yellow solid (10.7 g, 89%).

Workup

  1. temperaturerefluxed for 2 h
  2. temperaturethen cooled to 35° C
  3. stirringthe mixture stirred
  4. temperatureat reflux for 2 h
  5. stirringthe mixture stirred
  6. temperatureunder reflux overnight
  7. temperatureThe mixture was cooled
  8. washthen washed with water (100 mL), hydrochloric acid (2M; 150 mL), water (50 mL), sat. aq. NaHCO3 (100 mL), water (50 mL) and brine (50 mL)
  9. dry with materialAfter drying (MgSO4) the solution
  10. concentrationwas concentrated
  11. customto give crude product which
  12. customwas purified by silica column chromatography (silica 40-63 micron)
  13. washeluting with hexane:ethyl acetate (19:1 to 4:1)

Sources & evidence

ORD record
ord-ab5c9865091c4662befc51349245f348
Source dataset
uspto-grants-2011_09
Patent number
US08017603B2

Reaction notes

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