Hydrogen Bromide → 3(R,S)-amino-5-cyclohexyl-1,3-dihydro-1-methyl-2H-1,4-benzodiazepin-2-one

HRID 235242Notes

Reaction equation

HRID 235242 reaction equation
C(OC([NH:11][CH:12]1[N:18]=[C:17]([CH:19]2[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]2)[C:16]2[CH:25]=[CH:26][CH:27]=[CH:28][C:15]=2[N:14]([CH3:29])[C:13]1=[O:30])=O)C1C=CC=CC=1.Br>C(OCC)C>[NH2:11][CH:12]1[N:18]=[C:17]([CH:19]2[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24]2)[C:16]2[CH:25]=[CH:26][CH:27]=[CH:28][C:15]=2[N:14]([CH3:29])[C:13]1=[O:30]

Participants

4

Reactant 2

HCID 260Hydrogen BromideHCID 152352853(R,S)-[(Benzyloxycarbonyl)amino]-5-cydohexyl-1,3-dihydro-1-methyl-2H-1,4-benzodiazepin-2-one

Product 1

HCID 111191973(R,S)-amino-5-cyclohexyl-1,3-dihydro-1-methyl-2H-1,4-benzodiazepin-2-oneYield 80%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

A mixture of 3(R,S)-[(benzyloxycarbonyl)amino]-5-cyclohexyl-1,3-dihydro-1-methyl-2H-1,4-benzodiazepin-2-one (3.0 g, 7.4 mmol) and hydrobromic acid (45% in acetic acid, 6.2 ml) was stirred for 1 h at room temperature under an atmosphere of nitrogen. The mixture was then diluted with cold anhydrous diethyl ether (40 ml) and it was stirred at 0° C. for 45 min. The white precipitate was collected by filtration, washed with cold diethyl ether (4×30 ml) and then dissolved in a mixture of water (30 ml) and aqueous sodium hydroxide (2M, 15 ml). The basic aqueous phase was extracted with ethyl acetate (3×70 ml) and the combined organic layers were washed with brine (30 ml), dried (Na2SO4) and concentrated. The residue was chromatographed on silica gel using 94:6, dichloromethane: methanol as the eluant, to afford the title compound (1.6 g, 80%) as pale pink solid. mp 133-136° C. 1H NMR (360 MHz, CDCl3)δ1.02-1.40 (4H, m), 1.47-1.56 (1H, m), 1.61-1.74 (3H, m), 1.84-1.91 (1H, m), 1.96-2.06 (1H, m), 2.17 (2H, br s), 2.70-2.80 (1H, m), 3.39 (3H, s), 4.29 (1H, s), 7.20-7.27 (2H, m), 7.44-7.54 (2H, m).

Workup

  1. stirringwas stirred at 0° C. for 45 min
  2. filtrationThe white precipitate was collected by filtration
  3. washwashed with cold diethyl ether (4×30 ml)
  4. dissolutiondissolved in a mixture of water (30 ml) and aqueous sodium hydroxide (2M, 15 ml)
  5. extractionThe basic aqueous phase was extracted with ethyl acetate (3×70 ml)
  6. washthe combined organic layers were washed with brine (30 ml)
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated
  9. customThe residue was chromatographed on silica gel using 94:6, dichloromethane

Sources & evidence

ORD record
ord-7458c56d492c4b1f8190b7aea2211a85
Source dataset
uspto-grants-1997_01
Patent number
US05597915

Reaction notes

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