Water → (3RS)-1,3-dihydro-5-phenyl-3-phthalimido-1-{2-((RS)-2-tetrahydropyranyloxy) ethyl}-2H-1,4-benzodiazepine-2-one

To a solution of (3RS)-1,3-dihydro-5-phenyl-3-phthalimido-2H-1,4-benzodiazepine-2-one (1.90 g) in N,N-dimethylformamide (30 ml) was added sodium hydride (62% suspension in mineral oil; 0.20 g) gradually with stirring under cooling in an ice-bath (<3° C.). The mixture was stirred for 10 minutes under the same conditions. To the resultant mixture was added 2-[(tetrahydropyran-2-yl)oxy] ethyl bromide (1.60 g) in one portion. The mixture was stirred at ambient temperature for one hour and at 45° C. for 4.5 hours and allowed to stand overnight. The resultant reaction mixture was poured into water and extracted with ethyl acetate twice. The extract was washed with water and dried over magnesium sulfate. Removal of the solvent gave light yellow powder, which was washed with a mixture of ethyl acetate and diethyl ether and collected by filtration to afford a mixture (1.48 g) of (3RS)-1,3-dihydro-5-phenyl-3-phthalimido-1-{2 -((RS)-2-tetrahydropyranyloxy)ethyl}-2H-1,4-benzodiazepine-2-one and (3RS)-1,3-dihydro-5-phenyl-3-phthalimido-1-{2-((SR)-2-tetrahydropyranyloxy)ethyl}-2H-1,4-benzodiazepine-2one.

1. temperatureunder cooling in an ice-bath (<3° C.)
2. stirringThe mixture was stirred for 10 minutes under the same conditions
3. stirringThe mixture was stirred at ambient temperature for one hour and at 45° C. for 4.5 hours
4. customThe resultant reaction mixture
5. extractionextracted with ethyl acetate twice
6. washThe extract was washed with water
7. dry with materialdried over magnesium sulfate
8. customRemoval of the solvent
9. customgave light yellow powder, which
10. washwas washed with a mixture of ethyl acetate and diethyl ether
11. filtrationcollected by filtration

ORD-Eintrag

ord-1f56f44fb867438a84ee216c5acbaa44

Quelldatensatz

uspto-grants-1995_01

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US05382664