Hydrochloric Acid → 5-(2,2-Difluoro-ethoxy)-pyridine-2-carboxylic acid
Reaction equation
C[O:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([OH:11])=[CH:7][N:6]=1)=[O:4].C(=O)([O-])[O-].[Cs+].[Cs+].FC(F)(F)S(O[CH2:24][CH:25]([F:27])[F:26])(=O)=O.[Li+].[OH-].Cl>C(OCC)(=O)C.C1COCC1.CN(C=O)C>[F:26][CH:25]([F:27])[CH2:24][O:11][C:8]1[CH:9]=[CH:10][C:5]([C:3]([OH:2])=[O:4])=[N:6][CH:7]=1Participants
Reactant 5
Product 1
Reagents, catalysts & solvents 3
Procedure
To a mixture of 5-hydroxy-2-pyridinecarboxylic acid methyl ester (0.253 mL, 2.122 mmol), cesium carbonate (1.11 g, 3.40 mmol) and DMF (4.25 mL) was added 2,2-difluoroethyl trifluoromethanesulfonate (0.682 mL, 3.18 mmol). The reaction was stirred at ambient temperature for 3 hrs. The reaction was partitioned between water and ethyl acetate. The organic portion was concentrated and the residue was treated with 5 mL of THF and LiOH (Aq. 2N) (3.18 mL, 6.37 mmol). The reaction was stirred at ambient temperature for 16 hrs. The reaction was treated with 6N HCl until the pH reached ˜2 and then diluted with ethyl acetate. The organic portion was dried over Na2SO4, filtered and concentrated in vacuo to give the title compound (370 mg, 1.821 mmol, 86%) as a tan solid. MS m/z=204.1 (M+H).
Workup
- customThe reaction was partitioned between water and ethyl acetate
- concentrationThe organic portion was concentrated
- stirringThe reaction was stirred at ambient temperature for 16 hrs
- dry with materialThe organic portion was dried over Na2SO4
- filtrationfiltered
- concentrationconcentrated in vacuo
Sources & evidence
- ORD record
- ord-1f8d6b87180d4c1385d8506b93e2946f
- Source dataset
- uspto-grants-2016_04
- Patent number
- US09309263B2
Reaction notes
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