Triethylamine → Ethyl 3-(pyridin-2-yl)isoxazole-5-carboxylate

HRID 1506444Notes

Reaction equation

HRID 1506444 reaction equation
[OH:1]/[N:2]=[C:3](\Cl)/[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][N:5]=1.[C:11]([O:15][CH2:16][CH3:17])(=[O:14])[C:12]#[CH:13].C(N(CC)CC)C>ClCCl.O.C(OCC)(=O)C>[N:5]1[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=1[C:3]1[CH:13]=[C:12]([C:11]([O:15][CH2:16][CH3:17])=[O:14])[O:1][N:2]=1

Participants

7

Reactant 3

HCID 8471Triethylamine2×HCID 12182Ethyl propiolateHCID 135440287N-Hydroxypicolinimidoyl chloride

Product 1

HCID 58062833Ethyl 3-(pyridin-2-yl)isoxazole-5-carboxylateYield 89%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a suspension of the (Z)—N-hydroxypicolinimidoyl chloride (Preparation 63A, 8.00 g, 51.1 mmol) in dichloromethane (75 mL) in a three neck 1000 mL flask immersed in water and equipped with an addition funnel and thermometer was added ethyl propiolate (5.21 mL, 51.1 mmol). A mixture of triethylamine (8.55 mL, 61.3 mmol) and dichloromethane (20 mL) were added to the addition funnel and then slowly added to the reaction dropwise so that the temperature remained between 20 and 28° C. (by adding ice to the water bath). After the triethylamine was completely added, the reaction was stirred at room temperature for 2 h. The reaction mixture was diluted with ethyl acetate (350 mL), washed with water, and washed with brine. The combined aqueous layers were extracted with ethyl acetate, and the combined organic layers were dried over anhydrous magnesium sulfate. Concentration under reduced pressure followed by purification on silica gel using a 20% mixture of ethyl acetate in hexane afforded ethyl 3-(pyridin-2-yl)isoxazole-5-carboxylate (9.90 g, 45.4 mmol, 89% yield) as an off white solid. 1H NMR (400 MHz, CDCl3) δ ppm 1.44 (t, 3H), 4.47 (q, J=7.26 Hz, 2H), 7.39 (ddd, J=7.59, 4.84, 1.21 Hz, 1H), 7.59 (s, 1H), 7.83 (td, J=7.81, 1.76 Hz, 1H), 8.13 (dt, J=7.92, 1.10 Hz, 1H), and 8.71 (ddd, J=4.84, 1.76, 0.88 Hz, 1H).

Workup

  1. customequipped with an addition funnel
  2. additionwere added to the addition funnel
  3. additionslowly added to the reaction dropwise so that the temperature
  4. customremained between 20 and 28° C.
  5. washwashed with water
  6. washwashed with brine
  7. extractionThe combined aqueous layers were extracted with ethyl acetate
  8. dry with materialthe combined organic layers were dried over anhydrous magnesium sulfate
  9. concentrationConcentration under reduced pressure
  10. customfollowed by purification on silica gel using a 20% mixture of ethyl acetate in hexane

Sources & evidence

ORD record
ord-c3d383c0ca2d4271b8ab2e028d4de881
Source dataset
uspto-grants-2015_12
Patent number
US09216972B2

Reaction notes

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