Hydrochloric Acid → 1-(2-((tert-butyldimethylsilyl)oxy)ethyl)-7-chloro-3-(2-chlorobenzyl)-3,4-dihydro-1H-benzo[e][1,4]diazepine-2,5-dione

HRID 1186085Notes

Reaction equation

HRID 1186085 reaction equation
C([O:4][CH2:5][CH2:6][N:7]1[C:13]2[CH:14]=[CH:15][C:16]([Cl:18])=[CH:17][C:12]=2[C:11](=[O:19])[NH:10][CH:9]([CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=2[Cl:27])[C:8]1=[O:28])(=O)C.[OH-].[Na+].Cl.N1C=CN=C1.[Si:37](Cl)([C:40]([CH3:43])([CH3:42])[CH3:41])([CH3:39])[CH3:38]>O1CCCC1.C(OCC)(=O)C.CO>[Si:37]([O:4][CH2:5][CH2:6][N:7]1[C:13]2[CH:14]=[CH:15][C:16]([Cl:18])=[CH:17][C:12]=2[C:11](=[O:19])[NH:10][CH:9]([CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=2[Cl:27])[C:8]1=[O:28])([C:40]([CH3:43])([CH3:42])[CH3:41])([CH3:39])[CH3:38]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 795ImidazoleHCID 14798Sodium HydroxideHCID 28928tert-Butyldimethylsilyl chlorideHCID 670608182-(7-chloro-3-(2-chlorobenzyl)-2,5-dioxo-2,3,4,5-tetrahydro-1H-benzo[e][1,4]diazepin-1-yl)ethyl acetate

Product 1

HCID 670608491-(2-((tert-butyldimethylsilyl)oxy)ethyl)-7-chloro-3-(2-chlorobenzyl)-3,4-dihydro-1H-benzo[e][1,4]diazepine-2,5-dione

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To 2-(7-chloro-3-(2-chlorobenzyl)-2,5-dioxo-2,3,4,5-tetrahydro-1H-benzo[e][1,4]diazepin-1-yl)ethyl acetate (0.62 g, 1.47 mmol) suspended in tetrahydrofuran (10 mL) was added 2M aqueous sodium hydroxide (2.2 mL, 4.4 mmol). Methanol (2 mL) was added, which caused the solution to become homogeneous. The solution was stirred at ambient temperature for 2 hours, then acidified with 1M hydrochloric acid, partitioned between ethyl acetate and brine, separated, dried with sodium sulfate, filtered and concentrated in vacuo. The resulting solid was dissolved in N,N-dimethylformamide (10 mL), and imidazole (0.14 g, 2 mmol) was added followed by tert-butyldimethylsilyl chloride (0.24 g, 1.6 mmol). This mixture was stirred at ambient temperature overnight, then diluted with ethyl acetate, washed with 10% citric acid, water, and brine, dried with sodium sulfate, filtered and concentrated in the presence of silica gel. The product was purified by column chromatography eluting with a gradient of 0-50% ethyl acetate in hexanes to yield 1-(2-((tert-butyldimethylsilyl)oxy)ethyl)-7-chloro-3-(2-chlorobenzyl)-3,4-dihydro-1H-benzo[e][1,4]diazepine-2,5-dione.

Workup

  1. custompartitioned between ethyl acetate and brine
  2. customseparated
  3. dry with materialdried with sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. dissolutionThe resulting solid was dissolved in N,N-dimethylformamide (10 mL)
  7. stirringThis mixture was stirred at ambient temperature overnight
  8. washwashed with 10% citric acid, water, and brine
  9. dry with materialdried with sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated in the presence of silica gel
  12. customThe product was purified by column chromatography
  13. washeluting with a gradient of 0-50% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-87c797099be041b5a0ab9b051cb52fe1
Source dataset
uspto-grants-2014_03
Patent number
US08673897B2

Reaction notes

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