Dimethylformamide → 4-Methoxy-1-(2-trimethylsilanyl-ethoxymethyl)-indazole-5-carbaldehyde
Reaction equation
Br[C:2]1[C:3]([O:19][CH3:20])=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:18])([CH3:17])[CH3:16])[N:6]=[CH:5]2.C([Li])CCC.CN([CH:29]=[O:30])C>C1COCC1>[CH3:20][O:19][C:3]1[C:2]([CH:29]=[O:30])=[CH:10][CH:9]=[C:8]2[C:4]=1[CH:5]=[N:6][N:7]2[CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:18])([CH3:17])[CH3:16]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- -78 °C
Procedure
To a stirred solution of 5-bromo-4-methoxy-1-(2-trimethylsilanyl-ethoxymethyl)-indazole (179 mg, 0.50 mmol) in THF (5.0 mL) at −78° C. under a nitrogen atmosphere was added n-butyl lithium (2.5 M in hexanes, 220 μL, 0.55 mmol) dropwise. The mixture was stirred at −78° C. for 1 hour and then DMF (78 μL, 1.0 mmol) was added. The mixture was stirred at −78° C. for 30 min, then allowed to reach RT and stirred for a further 1 hour. The reaction mixture was quenched with water (5 mL), separated and extracted with ethyl acetate (2×20 mL). The combined organic layers were washed with brine (20 mL), dried (Na2SO4), filtered and concentrated in vacuo. The resulting residue was subjected to flash chromatography (SiO2, 20% ethyl acetate in cyclohexane) to give the title compound as a yellow oil (78 mg, 51%). LCMS (Method B): RT=4.55 min, [M+H]+=307.
Workup
- stirringThe mixture was stirred at −78° C. for 30 min
- customto reach RT
- stirringstirred for a further 1 hour
- customThe reaction mixture was quenched with water (5 mL)
- customseparated
- extractionextracted with ethyl acetate (2×20 mL)
- washThe combined organic layers were washed with brine (20 mL)
- dry with materialdried (Na2SO4)
- filtrationfiltered
- concentrationconcentrated in vacuo
Sources & evidence
- ORD record
- ord-18b68ae1996046cea5323fae8c5cfb5c
- Source dataset
- uspto-grants-2013_10
- Patent number
- US08546376B2
Reaction notes
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