1,4-Benzodioxan → 2,3-Dihydro-1,4-benzodioxine-6-sulfonyl chloride

Temperature

20 °C

Chlorosulfonic acid (6 mL, 90 mmol) was added dropwise to an ice cooled solution of 1,4-benzodioxane (12 gm, 88 mmol) in chloroform (40 mL). After allowing the reaction mixture to warm to 20° C. (about 15 min.), this solution was poured on to ice (400 gm) and the product extracted into chloroform. This extract was dried (MgSO4) and the solvent evaporated to give the 6-chlorosulfonyl-1,4-benzodioxane as a white crystalline solid. This sulfonyl chloride was dissolved in methylene chloride (100 mL) and added to an ice cooled solution of 4-amino-1-butanol (10 gm, 112 mmol) and excess triethylamine (25 mL) in methylene chloride (250 mL). After stirring for 24 hours and gradually warming to ambient temp., the reaction mixture was washed with 6N HCl (100 mL), dried (MgSO4) and filtered. To this resulting solution was added 3,4-dihydro-2H-pyran (20 mL, 219 mmol) and p-toluenesulfonic acid (100 mg) and additional methylene chloride to bring the volume to 300 mL. After stirring at ambient temp. for 15-20 hours, the solution was washed with saturated aq. Na2CO3 (100 mL), dried (MgSO4) and the solvent evaporated. The oily residue was chromatographed on a column of silica gel and eluted with 30% ethyl acetate/hexane to give the purified product as a colorless oil.

1. extractionthe product extracted into chloroform
2. dry with materialThis extract was dried (MgSO4)
3. customthe solvent evaporated

ORD record

ord-03204d473f564e5da354a0e7ed77cd98

Source dataset

uspto-grants-1999_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05952351