Hydrochloric Acid → Methyl 4-acetyl-5-phenylisoxazole-3-carboxylate

Temperature

100 °C

A solution of methyl 4-bromo-5-phenylisoxazole-3-carboxylate (358 mg, 1.269 mmol, prepared in a similar manner as described in step 9-B) and tributyl(1-ethoxyvinyl)tin (0.858 mL, 2.54 mmol) in dioxane (5 mL) was heated at 100° C. for 24 h. To the reaction mixture was added 1N aqueous hydrochloric acid (2.54 mL, 2.54 mmol), and the mixture was stirred at room temperature for 1 h. The reaction mixture was diluted with ethyl acetate (100 mL), washed with water (30 mL), washed with a saturated aqueous solution of sodium bicarbonate (30 mL), and washed with brine (30 mL). The mixture was concentrated to ˜5 mL, and potassium fluoride (0.059 mL, 2.54 mmol) in 2 mL of water was added, and the mixture was stirred for 10 minutes. The solid was filtered and washed with ethyl acetate, and the filtrate was washed with water (10 mL), washed with brine (10 mL), and dried over anhydrous sodium sulfate. Concentration followed by purification by silica gel chromatography with hexanes/ethyl acetate (10/1) afforded methyl 4-acetyl-5-phenylisoxazole-3-carboxylate (105 mg). The compound had an HPLC ret. time=2.69 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: M+1=246+.

1. washwashed with water (30 mL)
2. washwashed with a saturated aqueous solution of sodium bicarbonate (30 mL)
3. washwashed with brine (30 mL)
4. additionwas added
5. stirringthe mixture was stirred for 10 minutes
6. filtrationThe solid was filtered
7. washwashed with ethyl acetate
8. washthe filtrate was washed with water (10 mL)
9. washwashed with brine (10 mL)
10. dry with materialdried over anhydrous sodium sulfate
11. concentrationConcentration
12. customfollowed by purification by silica gel chromatography with hexanes/ethyl acetate (10/1)

ORD record

ord-5385b7b5d1114d12932d3ddfd75acdf5

Source dataset

uspto-grants-2013_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08354398B2