Sodium hydride → (4R)-1-[(6-Bromopyridin-2-yl)methyl]-4-{[tert-butyl(dimethyl)silyl]oxy}pyrrolidin-2-one
Reaction equation
[Si:1]([O:8][C@H:9]1[CH2:13][NH:12][C:11](=[O:14])[CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[H-].[Na+].[Br:17][C:18]1[CH:23]=[CH:22][CH:21]=[C:20]([CH2:24]Br)[N:19]=1>O1CCCC1>[Br:17][C:18]1[N:19]=[C:20]([CH2:24][N:12]2[CH2:13][C@H:9]([O:8][Si:1]([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2])[CH2:10][C:11]2=[O:14])[CH:21]=[CH:22][CH:23]=1Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 0 °C
Procedure
(4R)-4-{[tert-Butyl(dimethyl)silyl]oxy}pyrrolidin-2-one (1.08 g, 5.02 mmol) was dissolved in tetrahydrofuran (21.13 mL) and cooled to 0° C. Sodium hydride (0.23 g, 5.86 mmol) was added and the solution was allowed to stir for 15 minutes. In a separate flask, 2-bromo-6-(bromomethyl)pyridine (Example 190, Step 1) (1.05 g, 4.18 mmol) was dissolved in THF (10.57 mL) and cooled to 0° C., and added dropwise to the reaction mixture. The solution was stirred for 15 minutes at 0° C. and then at room temperature. The reaction mixture was quenched with water, and the product extracted with ethyl acetate. The combined organic layers were dried over magnesium sulfate, filtered and concentrated to afford the title compound which was used without further purification.
Workup
- temperaturecooled to 0° C.
- additionadded dropwise to the reaction mixture
- stirringThe solution was stirred for 15 minutes at 0° C.
- customat room temperature
- customThe reaction mixture was quenched with water
- extractionthe product extracted with ethyl acetate
- dry with materialThe combined organic layers were dried over magnesium sulfate
- filtrationfiltered
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-b6288326100c4b6482c7745536522a06
- Source dataset
- uspto-grants-2013_02
- Patent number
- US08367706B2
Reaction notes
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