Potassium Carbonate → 6-Chloro-5-(1,1-dioxido-isothiazolidin-2-yl)-pyridine-2-carboxylic acid methyl ester

HRID 632090Notes

Reaction equation

HRID 632090 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:10]=[CH:9][C:8](Br)=[C:7]([Cl:12])[N:6]=1)=[O:4].[S:13]1(=[O:19])(=[O:18])[CH2:17][CH2:16][CH2:15][NH:14]1.N1C=CC=CC=1C(=O)CC(C1C=CC=CN=1)=O.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.[Cu]I.O>[CH3:1][O:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([N:14]2[CH2:15][CH2:16][CH2:17][S:13]2(=[O:19])=[O:18])=[C:7]([Cl:12])[N:6]=1)=[O:4]

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 6421571,3-PropanesultamHCID 27284941,3-Di(2-pyridyl)-1,3-propanedioneHCID 46311197Methyl 5-bromo-6-chloropicolinate

Product 1

HCID 866747566-Chloro-5-(1,1-dioxido-isothiazolidin-2-yl)-pyridine-2-carboxylic acid methyl esterYield 41.4%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

Under a nitrogen atmosphere, a solution of 5-bromo-6-chloro-pyridine-2-carboxylic acid methyl ester (Example 9 c, 1 g, 4 mmol), isothiazolidine 1,1-dioxide (730 mg, 06 mmol), copper(I) iodide (150 mg, 0.8 mmol), 1,3-di(pyridin-2-yl)propane-1,3-dione (CAN 10198-89-7, 180 mg, 0.8 mmol) and potassium carbonate (1.1 g, 8 mmol) in DMF (20 mL) was reacted for 24 h at 110° C. The reaction mixture was poured into water, and extracted with ethyl acetate (3×50 mL). The combined organic extracts were washed with water and brine, dried over anhydrous sodium sulfate and evaporated. The residue was purified by column chromatography (silica gel, 4 g, 10% ethyl acetate in petroleum ether) to yield the title compound (0.048 g, 1.6 mmol, 41.4%) as yellow solid; MS (EI): m/e=291.0 [M+H]+.

Workup

  1. extractionextracted with ethyl acetate (3×50 mL)
  2. washThe combined organic extracts were washed with water and brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. customevaporated
  5. customThe residue was purified by column chromatography (silica gel, 4 g, 10% ethyl acetate in petroleum ether)

Sources & evidence

ORD record
ord-847316ce285a44caa95f0b96e8dc3546
Source dataset
uspto-grants-2016_04
Patent number
US09321727B2

Reaction notes

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