Ammonium Chloride → (2S,5R)-2-[2-(2-Chloro-phenyl)-ethyl]-5-isopropyl-3,6-dimethoxy-2-methyl-2,5-dihydro-pyrazine
Reaction equation
[CH3:1][O:2][C:3]1[C@@H:4]([CH:12]([CH3:14])[CH3:13])[N:5]=[C:6]([O:10][CH3:11])[CH:7]([CH3:9])[N:8]=1.C([Li])(C)(C)C.Br[CH2:21][CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=1[Cl:29].[Cl-].[NH4+]>O1CCCC1>[Cl:29][C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=1[CH2:22][CH2:21][C@@:7]1([CH3:9])[C:6]([O:10][CH3:11])=[N:5][C@H:4]([CH:12]([CH3:14])[CH3:13])[C:3]([O:2][CH3:1])=[N:8]1Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Procedure
A solution of (R)-(−)-2,5-dihydro-3,6-dimethoxy-2-isopropyl-5-methylpyrazine (1.0 g, 5.0 mmol) in tetrahydrofuran (23 ml) was cooled to −70° C., then tert.butyllithium (1.7 M in pentane, 3.26 ml, 5.55 mmol) was added and the mixture was stirred for 1 hour. A solution of 1-(2-bromo-ethyl)-2-chlorobenzene (1.44 g, 6.56 mmol) in tetrahydrofuran (10 ml) was added slowly and the mixture was stirred overnight at −70° C. At room temperature saturated ammonium chloride solution was added and the mixture was extracted three times with ether. The combined organic layers were dried (MgSO4), filtered and evaporated. The residue was purified by column chromatography (SiO2, heptane/EtOAc=1:1 to yield an orange solid, (1.22 g, 72%); MS (ISP): 337.1; 339.1 ((M+H)+.).
Workup
- stirringthe mixture was stirred overnight at −70° C
- extractionthe mixture was extracted three times with ether
- dry with materialThe combined organic layers were dried (MgSO4)
- filtrationfiltered
- customevaporated
- customThe residue was purified by column chromatography (SiO2, heptane/EtOAc=1:1
- customto yield an orange solid, (1.22 g, 72%)
Sources & evidence
- ORD record
- ord-1f8d0e6aa34744169bd4ce39625a625d
- Source dataset
- uspto-grants-2013_12
- Patent number
- US08604061B2
Reaction notes
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