Sodium hydride → 5-bromo-2-methyl-4-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)methoxy)pyrimidine
Reaction equation
[CH3:1][C:2]1[CH:3]=[CH:4][C:5]([C@H:8]2[CH2:10][C@@H:9]2[CH2:11][OH:12])=[N:6][CH:7]=1.[H-].[Na+].[Br:15][C:16]1[C:17](Cl)=[N:18][C:19]([CH3:22])=[N:20][CH:21]=1.C(=O)(O)[O-].[Na+]>C1COCC1>[Br:15][C:16]1[C:17]([O:12][CH2:11][C@H:9]2[CH2:10][C@@H:8]2[C:5]2[CH:4]=[CH:3][C:2]([CH3:1])=[CH:7][N:6]=2)=[N:18][C:19]([CH3:22])=[N:20][CH:21]=1Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Procedure
To a solution ((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)methanol (1.58 g, 9.7 mmol) in THF (25 mL) was added sodium hydride (466 mg, 11.6 mmol). The reaction mixture stirred at ambient temperature for 30 minutes. Next, a solution of 5-bromo-4-chloro-2-methylpyrimidine (2.0 g, 9.7 mmol) in THF (10 mL) was added and the reaction mixture was stirred at ambient temperature for two hours. Aqueous sodium bicarbonate (20 mL) was carefully added and the mixture was extracted with EtOAc (2×50 mL). The combined organics were dried over MgSO4, filtered and concentrated to the resulting residue, which was purified by column chromatography on silica gel (10% to 50% EtOAc in hexanes) to afford the title compound as a yellow solid. LC/MS m/z=334.1 (M+H)+.
Workup
- stirringthe reaction mixture was stirred at ambient temperature for two hours
- extractionthe mixture was extracted with EtOAc (2×50 mL)
- dry with materialThe combined organics were dried over MgSO4
- filtrationfiltered
- concentrationconcentrated to the resulting residue, which
- customwas purified by column chromatography on silica gel (10% to 50% EtOAc in hexanes)
Sources & evidence
- ORD record
- ord-1128003b3c1244e58b40677b881f6890
- Source dataset
- uspto-grants-2016_03
- Patent number
- US09273033B2
Reaction notes
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