Toluene → 5-(2,2-Dimethyl-propyl)-isoxazole-3-carbaldehyde

Temperature

-78 °C

To a solution of 5-(2,2-dimethyl-propyl)-isoxazole-3-carbonitrile (821 mg, 5 mmol) in Et2O (15 mL) and n-hexane (50 mL) was added dropwise at −78° C. an 1.7M toluene solution of DIBAL (11.8 mL, 20 mmol) keeping the temperature below −70° C. The mixture was stirred at −78° C. for 1 h. The reaction was quenched with EtOAc (7.5 mL), allowed to warm to 0° C., then sat. NH4Cl solution (25 mL) and 1M HCl (50 mL) were added and the mixture stirred at room temperature for 2 h. The layers were separated and the aqueous phase was extracted with EtOAc. The combined organic phases were dried over Na2SO4, filtered and concentrated. The crude product was purified by column chromatography on silica gel (cyclohexane to cyclohexane-EtOAc 80:20) to furnish title compound as a colorless oil: TLC (cyclohexane-EtOAc 80:20) Rf=0.44; ESIMS [M+H]+=168; 1H NMR (400 MHz, DMSO-d6): δ 10.06 (s, 1H), 6.66 (s, 1H), 2.74 (s, 2H), 0.92 (s, 9H).

1. customthe temperature below −70° C
2. customThe reaction was quenched with EtOAc (7.5 mL)
3. temperatureto warm to 0° C.
4. additionsat. NH4Cl solution (25 mL) and 1M HCl (50 mL) were added
5. stirringthe mixture stirred at room temperature for 2 h
6. customThe layers were separated
7. extractionthe aqueous phase was extracted with EtOAc
8. dry with materialThe combined organic phases were dried over Na2SO4
9. filtrationfiltered
10. concentrationconcentrated
11. customThe crude product was purified by column chromatography on silica gel (cyclohexane to cyclohexane-EtOAc 80:20)

ORD record

ord-2fe050ce8a424b02baf92641134a58a0

Source dataset

uspto-grants-2012_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08093406B2