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

HRID 1490100Notes

Reaction equation

HRID 1490100 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 79.7%

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) and hydrobromic acid (45% in acetic acid; 6.2 ml) was stirred for 1 hour at room temperature under a nitrogen atmosphere. The mixture was then diluted with cold anhydrous diethyl ether (40 ml) and it was stirred at 0° C. for 45 minutes. 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 2N sodium hydroxide (15 ml). The basic aqueous phase was extracted with ethyl acetate (3×70 ml) and the combined organic solutions were washed with brine (1×30 ml), dried (Na2SO4) and concentrated. Flash chromatography of the remaining pale red oil (silica gel, dichloromethane-methanol, 94:6) gave the title compound (1.6 g) as a waxy solid; δH (250 MHz, CDCl3) 7.53-7.45 (2H, m), 7.28-7.20 (2H, m), 4.30 (1H, s), 3.39 (3H, s), 2.75 (1H, m), 2.04-1.03 (10H, m); m/z (CI) 272 (M+ +1).

Workup

  1. stirringwas stirred at 0° C. for 45 minutes
  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 2N sodium hydroxide (15 ml)
  5. extractionThe basic aqueous phase was extracted with ethyl acetate (3×70 ml)
  6. washthe combined organic solutions were washed with brine (1×30 ml)
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-f1b5d5ae40cd4b45a3a490f5f43c0837
Source dataset
uspto-grants-1997_10
Patent number
US05681833

Reaction notes

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