Triethylamine → Ethyl 5-phenyl-4-propionylisoxazole-3-carboxylate

Temperature

120 °C

To a solution of 1-phenylpent-1-yn-3-one (36.7 mg, 0.232 mmol) and triethylamine (0.113 mL, 0.812 mmol) in toluene (1 mL) at 120° C. was added (Z)-ethyl 2-chloro-2-(hydroxyimino)acetate (105 mg, 0.696 mmol) in toluene (1 mL) dropwise. The reaction mixture was stirred at 120° C. for 16 h. To the reaction mixture was added additional (Z)-ethyl 2-chloro-2-(hydroxyimino)acetate (105 mg, 0.696 mmol) and triethylamine (0.113 mL, 0.812 mmol), and the reaction mixture was stirred at 140° C. for 3 days. The reaction mixture was concentrated, diluted with ethyl acetate (5 mL), washed with water (1 mL), washed with a saturated aqueous solution of sodium bicarbonate (1 mL), washed with brine (1 mL), and dried over anhydrous sodium sulfate. Concentration followed by purification by silica gel chromatography with hexanes/ethyl acetate (10/1) afforded ethyl 5-phenyl-4-propionylisoxazole-3-carboxylate (14.7 mg). The compound had an HPLC ret. time=3.15 min.−Column: YMC S5 COMBISCREEN® 4.6×50 mm; Gradient time: 4 min; Flow rate=4 ml/min; Solvent A=10% MeOH−90% Water−0.2% H3PO4; Solvent B=90% MeOH−10% water−0.2% H3PO4; Start % B=0; Final % B=100. LC-MS: 274+.

1. stirringthe reaction mixture was stirred at 140° C. for 3 days
2. concentrationThe reaction mixture was concentrated
3. additiondiluted with ethyl acetate (5 mL)
4. washwashed with water (1 mL)
5. washwashed with a saturated aqueous solution of sodium bicarbonate (1 mL)
6. washwashed with brine (1 mL)
7. dry with materialdried over anhydrous sodium sulfate
8. concentrationConcentration
9. customfollowed by purification by silica gel chromatography with hexanes/ethyl acetate (10/1)

ORD record

ord-9cc3d6825e6a439eae37ebb930cfb72d

Source dataset

uspto-grants-2013_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08354398B2