Triethylamine → Ethyl 3-(3-fluorophenyl)-5-methylisoxazole-4-carboxylate

HRID 1897099Notes

Reaction equation

HRID 1897099 reaction equation
[OH:1]/[N:2]=[C:3](\Cl)/[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([F:10])[CH:5]=1.[C:12]([O:17][CH2:18][CH3:19])(=[O:16])[C:13]#[C:14][CH3:15].C(N(CC)CC)C>C(OCC)C>[CH2:18]([O:17][C:12]([C:13]1[C:3]([C:4]2[CH:9]=[CH:8][CH:7]=[C:6]([F:10])[CH:5]=2)=[N:2][O:1][C:14]=1[CH3:15])=[O:16])[CH3:19]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 78043Ethyl 2-butynoateHCID 142213383-fluoro-N-hydroxybenzene-1-carbonimidoyl chloride

Product 1

HCID 22309060Ethyl 3-(3-fluorophenyl)-5-methylisoxazole-4-carboxylateYield 39.5%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

To a solution of (E)- and/or (Z)—N-hydroxy-3-fluoro-benzenecarboximidoyl chloride (11.1 g, 64 mmol) in diethylether (151 mL) was added ethyl 2-butynoate (7.2 g, 7.5 mL, 64 mmol) at 0° C. followed by the dropwise addition of triethylamine (7.8 g, 10.7 mL, 77 mmol) and the resulting mixture allowed to warm up to room temperature overnight. The mixture was then poured onto ice-water, and extracted with diethylether. The combined organic layers were then washed with water and brine, dried over sodium sulfate and evaporated. Purification by chromatography (SiO2, heptane:ethyl acetate=100:0 to 1:1) afforded the title compound (6.3 g, 39%) which was obtained as a white solid. MS: m/e=250.1 [M+H]+.

Workup

  1. additionThe mixture was then poured onto ice-water
  2. extractionextracted with diethylether
  3. washThe combined organic layers were then washed with water and brine
  4. dry with materialdried over sodium sulfate
  5. customevaporated
  6. customPurification by chromatography (SiO2, heptane:ethyl acetate=100:0 to 1:1)

Sources & evidence

ORD record
ord-70e49e3ef5b64703952485e5e27fc771
Source dataset
uspto-grants-2013_08
Patent number
US08518974B2

Reaction notes

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