Reaction #368151

Reaction equation

tert-butyl 3(S)-[7-(1-benzyloxycarbonyl-4-piperidyl)-1(S)-ethoxycarbonylheptyl]amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzoxazepine-5-acetate

hydrogen bromide acetic acid

→

3(S)-[1(S)-carboxy-7-(4-piperidyl)heptyl]amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzoxazepine-5-acetic acid

Yield 63.1%

Solvents

ethyl ether

acetic acid

Conditions

Workup

1. 1
   OtherThe supernatant layer is removed by decantation
2. 2
   workup.DISSOLUTIONthe precipitate is dissolved in 1N sodium hydroxide solution (10 ml)
3. 3
   workup.WAITto stand for 30 minutes at room temperature
4. 4
   workup.ADDITIONAfter addition of acetic acid (2 ml)
5. 5
   Otherthe mixture is chromatographed on MCI gel
6. 6
   ConcentrationThe eluate is concentrated in vacuo

Procedure

To a solution of tert-butyl 3(S)-[7-(1-benzyloxycarbonyl-4-piperidyl)-1(S)-ethoxycarbonylheptyl]amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzoxazepine-5-acetate (0.35 g) in acetic acid (1.5 ml) is added 30% hydrogen bromide-acetic acid solution (1.5 ml). The resulting mixture is allowed to stand for 0.5 hour at room temperature and then diluted with ethyl ether (100 ml). The supernatant layer is removed by decantation and the precipitate is dissolved in 1N sodium hydroxide solution (10 ml). The solution is allowed to stand for 30 minutes at room temperature. After addition of acetic acid (2 ml), the mixture is chromatographed on MCI gel using water-methanol (1:1) as an eluent. The eluate is concentrated in vacuo and lyophilized to give 3(S)-[1(S)-carboxy-7-(4-piperidyl)heptyl]amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzoxazepine-5-acetic acid (0.15 g) as colorless powder.

Source