Sodium hydride → 6-Cyclopropylmethoxy-5-(1,1-dioxido-isothiazolidin-2-yl)-pyridine-2-carboxylic acid

HRID 927477Notes

Reaction equation

HRID 927477 reaction equation
[H-].[Na+].C[O:4][C:5]([C:7]1[CH:12]=[CH:11][C:10]([N:13]2[CH2:17][CH2:16][CH2:15][S:14]2(=[O:19])=[O:18])=[C:9](Cl)[N:8]=1)=[O:6].[CH:21]1([CH2:24][OH:25])[CH2:23][CH2:22]1>>[CH:21]1([CH2:24][O:25][C:9]2[N:8]=[C:7]([C:5]([OH:4])=[O:6])[CH:12]=[CH:11][C:10]=2[N:13]2[CH2:17][CH2:16][CH2:15][S:14]2(=[O:19])=[O:18])[CH2:23][CH2:22]1

Participants

4

Reactant 3

HCID 24758Sodium hydrideHCID 75644CyclopropanemethanolHCID 866747566-Chloro-5-(1,1-dioxido-isothiazolidin-2-yl)-pyridine-2-carboxylic acid methyl ester

Product 1

HCID 710877116-Cyclopropylmethoxy-5-(1,1-dioxido-isothiazolidin-2-yl)-pyridine-2-carboxylic acidYield 46%

Procedure

Sodium hydride (0.029 g, 0.86 mmol) was added in portions to a solution of cyclopropanemethanol (CAN 2516-33-8, 20 mL) and the reaction mixture was stirred for 30 min at room temperature. 6-Chloro-5-(1,1-dioxido-isothiazolidin-2-yl)-pyridine-2-carboxylic acid methyl ester (0.050 g, 0.17 mmol) was added and the mixture was heated to 100° C. overnight, quenched with water and concentrated under reduced pressure. The residue was dissolved in water, extracted with ethyl acetate (50 mL). The pH of the aqueous layer was adjusted to 2 by addition of 1 N hydrochloric acid and subsequently extracted with ethyl acetate (3×20 mL). The combined extracts were washed with water and brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure to give the crude product. The crude product was purified by column chromatography (silica gel, 4 g, 33% ethyl acetate in petroleum ether) to yield the title compound (25 mg, 0.08 mmol, 46%) as yellow solid; MS (EI): m/e=313.1 [M+H]+.

Workup

  1. temperaturethe mixture was heated to 100° C. overnight
  2. customquenched with water
  3. concentrationconcentrated under reduced pressure
  4. dissolutionThe residue was dissolved in water
  5. extractionextracted with ethyl acetate (50 mL)
  6. additionThe pH of the aqueous layer was adjusted to 2 by addition of 1 N hydrochloric acid
  7. extractionsubsequently extracted with ethyl acetate (3×20 mL)
  8. washThe combined extracts were washed with water and brine
  9. dry with materialdried over anhydrous sodium sulfate
  10. concentrationconcentrated under reduced pressure
  11. customto give the crude product
  12. customThe crude product was purified by column chromatography (silica gel, 4 g, 33% ethyl acetate in petroleum ether)

Sources & evidence

ORD record
ord-ff47c23f59ec47c0bc2efbf960718b07
Source dataset
uspto-grants-2016_03
Patent number
US09290451B2

Reaction notes

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