Methyl isocyanide → Oxazole, 5-(diethoxymethyl)-

Temperature

-78 °C

Prepared according to the procedure of Schollkopf (J. Am. Chem. Soc. 112 (10) 4070 (1990)). To a solution of methyl isocyanide (2.88 g, 0.0702 mol) in THF (50 mL) under argon at -78° C. was added dropwise n-butyllithium solution (1.6M in hexanes, 44 mL) over 15 mins. After stirring for an additional 20 mins at -78° C., a solution of ethyl diethoxyacetate (12.62 g, 0.0702 mol) in THF (15 mL) was added dropwise over 20 mins. The bath was allowed to warm to -30° C. over the next 2 hrs and the reaction was then stirred at 0° C. for 30 mins. The reaction was quenched at 0° C. with glacial HoAc (4.22 g, 0.0702 mol) and the solvent was removed by rotary evaporation in vacuo. The golden solid was partitioned with H2O (45 mL) and EtOAc (200 mL), and the aqueous extracted with EtOAc (2×200 mL). The combined organic was washed with satd aq NaCl, dried over Na2SO4, and concentrated in vacuo to a brown oil. Chromatography on a 300 g SiO2 flash column with a gradient of EtOAc/hexane (10%, 15%, 20%) afforded the desired compound as a colorless liquid (7.46 g, 0.0436 mol, 62%): 1H NMR (CDCl3) δ1.25 (t, J=6.9 Hz, 6H), 3.56-3.70 (m, 4H), 5.62 (s, 1H), 7.26 (s, 1H), 7.86 (s, 1H). Mass spectrum: (M+H)+ =172.

1. customPrepared
2. temperatureto warm to -30° C. over the next 2 hrs
3. stirringthe reaction was then stirred at 0° C. for 30 mins
4. customThe reaction was quenched at 0° C. with glacial HoAc (4.22 g, 0.0702 mol)
5. customthe solvent was removed by rotary evaporation in vacuo
6. customThe golden solid was partitioned with H2O (45 mL) and EtOAc (200 mL)
7. extractionthe aqueous extracted with EtOAc (2×200 mL)
8. washThe combined organic was washed with satd aq NaCl
9. dry with materialdried over Na2SO4
10. concentrationconcentrated in vacuo to a brown oil

ORD record

ord-5bbb6b6aa3e04b238f75525318c0cacd

Source dataset

uspto-grants-1997_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05616720