Water → (R)-8,9-Dichloro-2,3,4,4a-Tetrahydro-1H-Pyrazino[1,2-a]Quinoxalin-5(6H)-One
Reaction equation
C([N:11]1[CH2:16][CH2:15][NH:14][C@@H:13]([C:17]([OH:19])=O)[CH2:12]1)(OCC1C=CC=CC=1)=O.[Cl:20][C:21]1[CH:26]=[C:25]([N+:27]([O-])=O)[CH:24]=[C:23](F)[C:22]=1[Cl:31].O.CN(C)C=O>C(N(CC)CC)C>[Cl:20][C:21]1[CH:26]=[C:25]2[C:24](=[CH:23][C:22]=1[Cl:31])[N:14]1[CH2:15][CH2:16][NH:11][CH2:12][C@@H:13]1[C:17](=[O:19])[NH:27]2Participants
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-228b338777cc42a19f11a04f7c3e4631
- Source dataset
- uspto-grants-2004_03
- Patent number
- US06706714B2
Reaction notes
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