1,2-Epoxybutane → 4-[(2-hydroxybutylamino)methyl]benzenesulfonamide Hydrochloride

To a mixed suspension of 4-aminomethylbenzenesulfonamide hydrochloride (4.45 g), methanol (20 ml) and THF (10 ml) was added N-ethyldiisopropylamine (5.2 ml) and then 1,2-epoxybutane (2.58 ml) was added, and the mixture was heated under reflux for 12 hrs. A 1N aqueous sodium hydroxide solution was added and the reaction mixture was basified and di-t-butyl carbonate (6.55 g) was added. The mixture was stirred at room temperature for 2 hrs. The solvent was evaporated under reduced pressure, and the residue was partitioned between water and ethyl acetate. The ethyl acetate layer was washed with 1N hydrochloric acid, aqueous sodium hydrogen carbonate and brine and dried by adding sodium sulfate. The solvent was evaporated under reduced pressure and the obtained residue was purified by silica gel column chromatography (n-hexane/ethyl acetate=7/3→1/1). To the obtained colorless amorphous form was added 4N hydrochloric acid ethyl acetate solution (10 ml), and the mixture was stirred at room temperature for 30 min. The solvent was evaporated under reduced pressure, toluene was added and the solvent was again evaporated under reduced pressure. Diisopropyl ether was added to the obtained residue and the mixture was crystallized to give the title compound (2.58 g, 46%).

1. temperaturethe mixture was heated
2. temperatureunder reflux for 12 hrs
3. customThe solvent was evaporated under reduced pressure
4. customthe residue was partitioned between water and ethyl acetate
5. washThe ethyl acetate layer was washed with 1N hydrochloric acid, aqueous sodium hydrogen carbonate and brine
6. customdried
7. additionby adding sodium sulfate
8. customThe solvent was evaporated under reduced pressure
9. customthe obtained residue was purified by silica gel column chromatography (n-hexane/ethyl acetate=7/3→1/1)
10. additionTo the obtained colorless amorphous form was added 4N hydrochloric acid ethyl acetate solution (10 ml)
11. stirringthe mixture was stirred at room temperature for 30 min
12. customThe solvent was evaporated under reduced pressure, toluene
13. additionwas added
14. customthe solvent was again evaporated under reduced pressure
15. additionDiisopropyl ether was added to the obtained residue
16. customthe mixture was crystallized

ORDレコード

ord-c2766f929b61427bab242b5f641cd364

出典データセット

uspto-grants-2008_07

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07402595B2