Hydrochloric Acid → 3-(5-Fluoro-pyridin-2-yl)-isoxazole-4-carboxylic acid ethyl ester

HRID 1521326Notes

Reaction equation

HRID 1521326 reaction equation
ClN1C(=O)CCC1=O.[F:9][C:10]1[CH:11]=[CH:12][C:13]([CH:16]=[N:17][OH:18])=[N:14][CH:15]=1.CN([CH:22]=[CH:23][C:24]([O:26][CH2:27][CH3:28])=[O:25])C.C(N(CC)CC)C.Cl>CN(C=O)C.C(Cl)(Cl)Cl>[CH2:27]([O:26][C:24]([C:23]1[C:16]([C:13]2[CH:12]=[CH:11][C:10]([F:9])=[CH:15][N:14]=2)=[N:17][O:18][CH:22]=1)=[O:25])[CH3:28]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 31398ChlorosuccinimideHCID 121015Ethyl 3-(N,N-dimethylamino)acrylateHCID 1363872515-Fluoro-pyridine-2-carbaldehyde oxime

Product 1

HCID 666436143-(5-Fluoro-pyridin-2-yl)-isoxazole-4-carboxylic acid ethyl esterYield 72%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of N-chlorosuccinimide (17.34 g, 130 mmol) in DMF (128 mL) was added 5-fluoro-pyridine-2-carbaldehyde oxime (18.2 g, 130 mmol) portionwise over 2 h at room temperature and as the reaction warmed up to 60° C. the mixture was cooled back to room temperature with an ice-water bath and the resulting mixture was then stirred for 64 h at room temperature. To this solution was then added ethyl 3-(N,N-dimethylamino)acrylate (18.6 g, 130 mmol) and triethylamine (36.2 mL, 260 mmol) in chloroform (64 mL) and the resulting mixture was then stirred for 1 h at room temperature and poured onto a mixture of ice water and HCl (4 N, 1 L) and extracted with ethylacetate. The organic extract was then washed with water, saturated aqueous sodium hydrogen carbonate solution, brine, dried with sodium sulfate, filtered and evaporated. Purification by chromatography (SiO2, heptane:ethylacetate=100:0 to 1:1) afforded the title product (21.96 g, 72%) which was obtained as a yellow solid. MS: m/e=237.1 [M+H]+.

Workup

  1. temperaturewas cooled back to room temperature with an ice-water bath
  2. extractionextracted with ethylacetate
  3. extractionThe organic extract
  4. washwas then washed with water, saturated aqueous sodium hydrogen carbonate solution, brine
  5. dry with materialdried with sodium sulfate
  6. filtrationfiltered
  7. customevaporated
  8. customPurification by chromatography (SiO2, heptane:ethylacetate=100:0 to 1:1)

Sources & evidence

ORD record
ord-418e65d708fe474a810ecd36c0b5e634
Source dataset
uspto-grants-2015_07
Patent number
US09073908B2

Reaction notes

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