Acetonitrile → 3-{3-[(7-{Benzyl[(2R)-2-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-2-hydroxyethyl]amino}heptyl)oxy]propyl}benzenesulfonamide

A mixture of (1R)-2-(benzylamino)-1-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)ethanol (55.8 g), 3-{3-[(7-bromoheptyl)oxy]propyl}benzenesulfonamide (63.65 g), N,N-diisopropylethylamine (55 ml) and acetonitrile (200 ml) was stirred and heated under N2 at reflux for ca 21 h. The mixture was cooled to room temperature then diethyl ether (1000 ml) and water (500 ml) were added and the mixture stirred. The organic phase was washed with water (500 ml), then saturated brine (500 ml) and dried (Na2SO4). The solution was concentrated and the product purified by chromatography on flash silica gel (1000 g), eluting with petroleum ether:ethyl acetate (ratios ranging successively from 4:1 to 1:1) to give the title compound (97.7 g)—LC RT=1.54 min. δ (DMSO-d6)—7.75 (2H, m), 7.45 (1H, t, J 8 Hz), 7.4 (1H, m), 7.35 (2H, s), 7.25 (5H, m), 7.05 (1H, d, J 8.5 Hz), 7.0 (1H, s), 6.7 (1H, d, J 8.5 Hz), 4.9 (1H, br s), 4.78 (2H, s), 4.6 (1H, m), 3.65 (1H, d, J 13.8 Hz), 3.55 (1H, d, J 13.8 Hz), 3.4 (1H, br s), 3.3 (4H, m), 2.7 (2H, m), 2.55 (2H, m), 2.4 (2H, m), 1.85 (2H, m), 1.45 (8H, m), 1.35 (2H, m), 1.25 (2H, m), 1.15 (4H, m).

1. temperatureheated under N2
2. temperatureat reflux for ca 21 h
3. stirringthe mixture stirred
4. washThe organic phase was washed with water (500 ml)
5. dry with materialsaturated brine (500 ml) and dried (Na2SO4)
6. concentrationThe solution was concentrated
7. customthe product purified by chromatography on flash silica gel (1000 g)
8. washeluting with petroleum ether

ORD-Eintrag

ord-c8f297ea4e4b42908c29b7014e0aac92

Quelldatensatz

uspto-grants-2008_10

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07442837B2