Dimethylformamide → 4-Chloro-5-fluoro-pyridine-3-carbaldehyde oxime
Reaction equation
[F:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[Cl:8].C([N-:12][CH:13](C)C)(C)C.[Li+].CN(C=[O:21])C.Cl.NO.C(=O)([O-])[O-].[K+].[K+]>C1COCC1>[Cl:8][C:7]1[C:2]([F:1])=[CH:3][N:4]=[CH:5][C:6]=1[CH:13]=[N:12][OH:21]Participants
Reactant 5
Product 1
Reagents, catalysts & solvents 1
Procedure
To a cooled (−78° C.) solution of 3-fluoro-4-chloro-pyridine (11.0 g, 84 mmol) in THF under nitrogen was added lithium diisopropylamide (1.8 M solution, 47 mL, 84 mmol) dropwise and the resultant solution stirred at −70 to −80° C. for 18 hours. DMF (7.68 g, 1.25 eq.) was added dropwise and stirring continued at −78° C. for 30 minutes before adding the reaction mixture to ice/2M HCl. The solution was extracted with diethyl ether and the organic layer back-extracted with 2M HCl, the two aqueous solutions held separately. The aqueous extracts were each treated with hydroxylamine hydrochloride (8.76 g, 126 mmol) and adjusted to pH 5 with potassium carbonate. After stirring for 1 hour the mixtures were extracted with ethyl acetate (×2), the combined organic extracts dried (Na2SO4), filtered and concentrated in vacuo to afford the title compound as a tan solid (11.07 g, 76%). LCMS (method B): RT=2.49 min, M+H+ 175.
Workup
- extractionThe solution was extracted with diethyl ether
- extractionthe organic layer back-extracted with 2M HCl
- stirringAfter stirring for 1 hour the mixtures
- extractionwere extracted with ethyl acetate (×2)
- dry with materialthe combined organic extracts dried (Na2SO4)
- filtrationfiltered
- concentrationconcentrated in vacuo
Sources & evidence
- ORD record
- ord-d3f4a7ce6d5148d7a79a59c71e07a624
- Source dataset
- uspto-grants-2010_12
- Patent number
- US07855216B2
Reaction notes
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