Ammonia → Aminobenzodiazepine

HRID 899398Notes

Reaction equation

HRID 899398 reaction equation
[NH3:1].C(=O)=O.[NH:5]1[C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[CH:9]=[CH:8][CH:7]=[N:6]1.CCOCC>C(Cl)Cl.CCO.CC(O)=O>[NH2:1][C:7]1[CH:8]=[CH:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[NH:5][N:6]=1

Participants

8

Reactant 4

HCID 222AmmoniaHCID 280Carbon DioxideHCID 3283Diethyl EtherHCID 134664Benzodiazepine

Product 1

HCID 21955614AminobenzodiazepineYield 47%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 702EthanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
-78 °C

Procedure

Ammonia (500 mL) was condensed with a dry ice condensor and maintained at −78° C. To this was added a solution of 6 (35 g, 91 mmol) in CH2Cl2 (600 mL). After 8 h, the dry ice condensor was removed and the reaction was warmed to room temperature allowing the ammonia to evaporate. The remaining solution was washed with brine, dried over anhydrous Na2SO4, filtered and concentrated to yield a white solid. This solid was dissolved in EtOH (500 mL) and AcOH (15 mL), and the resulting solution was refluxed for 24 h, and concentrated to yield a yellow-red oil. Addition of Et2O (300 mL) to this oil resulted in the precipitation of 8 (13 g, 47%) as a white powder: 1H NMR (300 MHz, CDCl3) δ 9.32 (s, 1 H), 7.83-7.05 (m, 8 H), 4.39 (s, 2 H); ESI MS m/z=305 [C15H11F3N2O+H]+.

Workup

  1. customthe dry ice condensor was removed
  2. temperaturethe reaction was warmed to room temperature
  3. customto evaporate
  4. washThe remaining solution was washed with brine
  5. dry with materialdried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto yield a white solid
  9. concentrationconcentrated
  10. customto yield a yellow-red oil

Sources & evidence

ORD record
ord-b99a57987ffe490eaa766212ffd9a916
Source dataset
uspto-grants-2008_04
Patent number
US07354914B2

Reaction notes

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