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

HRID 258090Notes

Reaction equation

HRID 258090 reaction equation
[C:1]1([C:7]2[C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=3[NH:11][C:10](=[O:18])[CH:9]([N:19]3[C:23](=[O:24])[C:22]4=[CH:25][CH:26]=[CH:27][CH:28]=[C:21]4[C:20]3=[O:29])[N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H-].[Na+].[O:32]1[CH2:37][CH2:36][CH2:35][CH2:34][CH:33]1[O:38][CH2:39][CH2:40]Br.O>CN(C)C=O>[C:1]1([C:7]2[C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=3[N:11]([CH2:40][CH2:39][O:38][CH:33]3[CH2:34][CH2:35][CH2:36][CH2:37][O:32]3)[C:10](=[O:18])[CH:9]([N:19]3[C:20](=[O:29])[C:21]4=[CH:28][CH:27]=[CH:26][CH:25]=[C:22]4[C:23]3=[O:24])[N:8]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 866212-(2-Bromoethoxy)tetrahydro-2H-pyranHCID 14800302(3RS)-1,3-dihydro-5-phenyl-3-phthalimido-2H-1,4-benzodiazepine-2-one

Product 1

HCID 14800303(3RS)-1,3-dihydro-5-phenyl-3-phthalimido-1-{2-((RS)-2-tetrahydropyranyloxy) ethyl}-2H-1,4-benzodiazepine-2-oneYield 58.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

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-2-one.

Workup

  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

Sources & evidence

ORD record
ord-82a78cfd2e1c4b89b383a469fd555d75
Source dataset
uspto-grants-1993_11
Patent number
US05264433

Reaction notes

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