Water → (R)-4-carbobenzyloxy-1-(4,5-dichloro-2-nitrophenyl)-piperazine-2-carboxylic acid
Reaction equation
[C:1]([N:11]1[CH2:16][CH2:15][NH:14][C@@H:13]([C:17]([OH:19])=[O:18])[CH2:12]1)([O:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:2].[Cl:20][C:21]1[CH:26]=[C:25]([N+:27]([O-:29])=[O:28])[CH:24]=[C:23](F)[C:22]=1[Cl:31].O.CN(C)C=O>C(N(CC)CC)C>[C:1]([N:11]1[CH2:16][CH2:15][N:14]([C:24]2[CH:23]=[C:22]([Cl:31])[C:21]([Cl:20])=[CH:26][C:25]=2[N+:27]([O-:29])=[O:28])[C@@H:13]([C:17]([OH:19])=[O:18])[CH2:12]1)([O:3][CH2:4][C:5]1[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=1)=[O:2]Participants
6
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 50 °C
Procedure
To a slurry containing 5.0 g of (R)-4-carbobenzyloxypiperazine-2-carboxylic acid, 4.2 g of 1,2-dichloro-fluoro-5-nitrobenzene, 85 mL of water and 170 mL of dimethylformamide is added slowly 5.3 mL of triethylamine. The solution is heated to 50° C. for 5 hours, then at ambient temperature overnight. The dark orange solution is concentrated under reduced pressure (1–2 mm, <50° C.) to an orange oily residue. This oil is dissolved in 400 mL of ethyl acetate and washed with 100 mL of 1 N HCl (2×), with 150 mL of water (2×), and 100 mL of brine. The organic layer is dried over MgSO4, filtered and concentrated to give 8.1 g (94.2%) of title compound as an orange solid foam.
Workup
- customat ambient temperature
- customovernight
- concentrationThe dark orange solution is concentrated under reduced pressure (1–2 mm, <50° C.) to an orange oily residue
- dissolutionThis oil is dissolved in 400 mL of ethyl acetate
- washwashed with 100 mL of 1 N HCl (2×), with 150 mL of water (2×), and 100 mL of brine
- dry with materialThe organic layer is dried over MgSO4
- filtrationfiltered
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-c3f0ffdbe3a147e5b8c4869da58c2e70
- Source dataset
- uspto-grants-2006_08
- Patent number
- US07098338B2
Reaction notes
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