Acetic Acid Mixture with Hydrobromic Acid → (S)-1-[N-(3,5-Dichlorophenyl)-N-phenylcarbamoyl]piperazine-2-carboxylic acid
Reaction equation
C(OC([N:11]1[CH2:16][CH2:15][N:14]([C:17](=[O:33])[N:18]([C:25]2[CH:30]=[C:29]([Cl:31])[CH:28]=[C:27]([Cl:32])[CH:26]=2)[C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[C@H:13]([C:34]([OH:36])=[O:35])[CH2:12]1)=O)C1C=CC=CC=1.Br.C(O)(=O)C>>[Cl:32][C:27]1[CH:26]=[C:25]([N:18]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[C:17]([N:14]2[CH2:15][CH2:16][NH:11][CH2:12][C@H:13]2[C:34]([OH:36])=[O:35])=[O:33])[CH:30]=[C:29]([Cl:31])[CH:28]=1Participants
Procedure
A mixture of 0.63 g (1.19 mmole) of (S)-4-(benzyloxycarbonyl)-1-[N-(3,5-dichlorophenyl)-N-phenylcarbamoyl]piperazine-2-carboxylic acid and 12 mL of 30% HBr/acetic acid was stirred at room temperature for 40 min, and residual HBr was then removed by bubbling nitrogen through the solution for 3 hr. The mixture was then concentrated in vacuo. The residue was treated with 25 mL of water and the pH adjusted to 7 with aqueous sodium hydroxide. To this mixture was added 45 mL of ethyl acetate, and the ethyl acetate layer was extracted with 5×25 mL of water. The combined water layers were treated with aqueous sodium hydroxide to adjust the pH to 7, and the aqueous was concentrated in vacuo to give 0.73 g of an oily solid, which was carried on immediately in Step F) below.
Workup
- customresidual HBr was then removed
- customby bubbling nitrogen through the solution for 3 hr
- concentrationThe mixture was then concentrated in vacuo
- additionThe residue was treated with 25 mL of water
- additionTo this mixture was added 45 mL of ethyl acetate
- extractionthe ethyl acetate layer was extracted with 5×25 mL of water
- additionThe combined water layers were treated with aqueous sodium hydroxide
- concentrationthe aqueous was concentrated in vacuo
Sources & evidence
- ORD record
- ord-9503e4ea35854f64af809b9db9cc0c57
- Source dataset
- uspto-grants-1994_09
- Patent number
- US05344830
Reaction notes
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