Cesium carbonate → (S)-methyl 6-(4-chlorophenyl)-5-(1,1,1-trifluoropropan-2-yloxy)pyrazine-2-carboxylate

HRID 1528365Notes

Reaction equation

HRID 1528365 reaction equation
Br[C:2]1[N:3]=[CH:4][C:5]([C:15]([O:17][CH3:18])=[O:16])=[N:6][C:7]=1[C:8]1[CH:13]=[CH:12][C:11]([Cl:14])=[CH:10][CH:9]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[F:25][C:26]([F:31])([F:30])[C@@H:27]([OH:29])[CH3:28]>CS(C)=O>[Cl:14][C:11]1[CH:12]=[CH:13][C:8]([C:7]2[N:6]=[C:5]([C:15]([O:17][CH3:18])=[O:16])[CH:4]=[N:3][C:2]=2[O:29][C@@H:27]([CH3:28])[C:26]([F:31])([F:30])[F:25])=[CH:9][CH:10]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 6999971(2S)-1,1,1-Trifluoropropan-2-olHCID 86619571Methyl 5-bromo-6-(4-chlorophenyl)pyrazine-2-carboxylate

Product 1

HCID 66678867(S)-methyl 6-(4-chlorophenyl)-5-(1,1,1-trifluoropropan-2-yloxy)pyrazine-2-carboxylateYield 77.6%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

To a solution of methyl 5-bromo-6-(4-chlorophenyl)pyrazine-2-carboxylate (0.847 g, 2.59 mmol, Eq: 1.00) in dry DMSO (8 ml) was added cesium carbonate (1.54 g, 2.84 mmol, Eq: 1.1) and (S)-1,1,1-trifluoro-2-propanol (324 mg, 233 μl, 2.84 mmol, Eq: 1.1) and the reaction mixture was stirred at room temperature for 3 hours. The reaction mixture was partitioned between water and ethyl acetate, the phases were separated and the organic phase was dried over MgSO4 evaporated and purified by flash chromatography (silica gel, 100 g, 10% to 50% EtOAc in heptane) to yield the title compound as light yellow oil (0.724 g, 77.6%), MS 361.1 (M+H)+.

Workup

  1. customThe reaction mixture was partitioned between water and ethyl acetate
  2. customthe phases were separated
  3. dry with materialthe organic phase was dried over MgSO4
  4. customevaporated
  5. custompurified by flash chromatography (silica gel, 100 g, 10% to 50% EtOAc in heptane)

Sources & evidence

ORD record
ord-6196277272494be9b10b49fe7fd590c7
Source dataset
uspto-grants-2015_07
Patent number
US09090599B2

Reaction notes

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