Ammonium Chloride → (2R,5S)-2-Isopropyl-3,6-dimethoxy-5-(4,4,4-trifluoro-3-phenyl-butyl)-2,5-dihydro-pyrazine
Reaction equation
[CH3:1][O:2][C:3]1[C@@H:4]([CH:11]([CH3:13])[CH3:12])[N:5]=[C:6]([O:9][CH3:10])[CH2:7][N:8]=1.C([Li])(C)(C)C.I[CH2:20][CH2:21][CH:22]([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[C:23]([F:26])([F:25])[F:24].[Cl-].[NH4+]>O1CCCC1>[CH:11]([C@@H:4]1[C:3]([O:2][CH3:1])=[N:8][C@@H:7]([CH2:20][CH2:21][CH:22]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[C:23]([F:25])([F:26])[F:24])[C:6]([O:9][CH3:10])=[N:5]1)([CH3:13])[CH3:12]Participants
6
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Procedure
A solution of (R)-(−)-2,5-dihydro-3,6-dimethoxy-2-isopropylpyrazine (1.1 g) in tetrahydrofuran (25 ml) was cooled to −70° C., then tert.butyllithium (1.7 M in pentane, 3.88 ml) was added and the mixture was stirred for 1 hour. A solution of (3-iodo-1-trifluoromethylpropyl)-benzene (1.98 g) in tetrahydrofuran (7 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=9:1 to yield a yellow liquid, (1.86 g, 83%).
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=9:1
- customto yield a yellow liquid, (1.86 g, 83%)
Sources & evidence
- ORD record
- ord-959df4cef5a74adc8a52051a4f39fecf
- Source dataset
- uspto-grants-2014_05
- Patent number
- US08729113B2
Reaction notes
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