4-Toluenesulfonyl chloride → HCID 19376853, compound

HRID 546167Notes

Reaction equation

HRID 546167 reaction equation
[CH2:1]([O:8][CH2:9][CH:10]([CH2:13][OH:14])[CH2:11]O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([Li])CCC.CCCCCC.C1(C)C=CC(S(Cl)(=O)=O)=CC=1.CC(C)([O-])C.[K+]>O1CCCC1.O>[CH2:1]([O:8][CH2:9][CH:10]1[CH2:11][O:14][CH2:13]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

8

Reactant 5

HCID 73974-Toluenesulfonyl chlorideHCID 8058HexaneHCID 102417822-benzyloxymethyl-propane-1,3-diolHCID 23665647Potassium tert-butoxideHCID 178418339Butyllithium

Product 1

HCID 19376853HCID 19376853, compoundYield 51%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
25 °C

Procedure

To a solution of 2-benzyloxymethyl-propane-1,3-diol (4.39 g, 22.36 mmol) in tetrahydrofuran (60 ml) stirred at −5° C., was added n-butyllithium in hexane (2.5 M, 11.18 ml, 27.96 mmol) and after 20 min, a solution of p-toluenesulfonyl chloride (5.12 g, 26.85 mmol) in tetrahydrofuran (20 ml) was added. The reaction was allowed to warm to 25° C. and then stirred for 2 h. To this solution was added water slowly and then extracted with ethyl acetate. The organics were dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was then dissolved in tert-butyl alcohol (90 ml) and potassium tert-butoxide (7.5 g, 66.83 mmol) was added, and the reaction was refluxed for 30 min and then stirred at 25° C. for 30 min. After such a time it was diluted with water (500 ml) and extracted with ether (2×250 ml). The extracts were combined and dried over magnesium sulfate, filtered and concentrated in vacuo. Purification on an AnaLogix Intelliflash system (120 g column, 20% ethyl acetate/hexanes to 30% ethyl acetate/hexanes) afforded 3-benzyloxymethyl-oxetane (2.02 g, 51%) as a light yellow oil: 1H NMR (300 MHz, CDCl3) δ ppm 3.19-3.32 (m, 1H, CH), 3.71 (d, J=6.9 Hz, 2H, OCH2), 4.42-4.48 (m, 2 H, 2×OCH of 2×OCH2), 4.55 (s, 2H, OCH2Ar), 4.77-4.83 (m, 2H, 2×OCH of 2×OCH2), 7.27-7.40 (m 5H, Ar).

Workup

  1. extractionextracted with ethyl acetate
  2. dry with materialThe organics were dried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. dissolutionThe residue was then dissolved in tert-butyl alcohol (90 ml)
  6. temperaturethe reaction was refluxed for 30 min
  7. stirringstirred at 25° C. for 30 min
  8. extractionextracted with ether (2×250 ml)
  9. dry with materialdried over magnesium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customPurification on an AnaLogix Intelliflash system (120 g column, 20% ethyl acetate/hexanes to 30% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-d8c8494bbe944a5490a0af1db0116f3e
Source dataset
uspto-grants-2011_05
Patent number
US07935699B2

Reaction notes

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