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

HRID 355682Notes

Reaction equation

HRID 355682 reaction equation
[CH:1]1([C:7]2[C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=3[NH:11][C:10](=[S:18])[CH:9]([NH:19]C(OCC3C=CC=CC=3)=O)[N:8]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.Br>C(Cl)Cl.C(O)(=O)C>[CH:1]1([C:7]2[C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=3[NH:11][C:10](=[S:18])[CH:9]([NH2:19])[N:8]=2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

5

Reactant 2

HCID 260Hydrogen BromideHCID 1357532921,3-Dihydro-5-cyclohexyl-3(R,S)-[(benzyloxycarbonyl)-amino]-2H-1,4-benzodiazepin-2-thione

Product 1

HCID 1357532931,3-dihydro-5-cyclohexyl-3(R,S)-amino-2H-1,4-benzodiazepin-2-thioneYield 93.2%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

1,3-Dihydro-5-cyclohexyl-3(R,S)-[(benzyloxycarbonyl)-amino]-2H-1,4-benzodiazepin-2-thione (787 mg, 1.93 mmole) was dissolved in 40 ml of a 1:1 mixture of methylene chloride and acetic acid. The resulting solution was cooled to 0° C. and a continuous stream of hydrogen bromide gas was passed into the stirred solution for 10 minutes. The reaction vessel was capped and the reaction mixture was allowed to warm to ambient temperature over 5 hours. All volatiles were removed under reduced pressure and the yellow residual solid was azeotropically dried with toluene. This material was partitioned between 180 ml of ethyl acetate and 7.3 ml of 10% sodium carbonate solution. The resulting suspension was stirred for 5 minutes and then filtered. The filter cake was washed with ethyl acetate, dried in vacuo over phosporus pentoxide (40° C.), and triturated with ethyl acetate-hexane (1:1) to give 492 mg of the title compound (93% yield).

Workup

  1. customThe reaction vessel was capped
  2. temperatureto warm to ambient temperature over 5 hours
  3. customAll volatiles were removed under reduced pressure
  4. dry with materialthe yellow residual solid was azeotropically dried with toluene
  5. customThis material was partitioned between 180 ml of ethyl acetate and 7.3 ml of 10% sodium carbonate solution
  6. filtrationfiltered
  7. washThe filter cake was washed with ethyl acetate
  8. customdried in vacuo over phosporus pentoxide (40° C.)
  9. customtriturated with ethyl acetate-hexane (1:1)

Sources & evidence

ORD record
ord-c40660d187bf4c92a4bd8f734db694e2
Source dataset
uspto-grants-1998_11
Patent number
US05834464

Reaction notes

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