Isobutyryl chloride → Methyl 5-isopropyloxazole-4-carboxylate

Temperature

-50 °C

To a solution of sodium methoxide (1.86 g) in DMF (30 ml) was added methyl isocyanoacetate (2.38 ml) dropwise at −50° C. and the mixture stirred for 30 min at −50° C. 2-Methylpropanoyl chloride (3.36 ml) was added gradually to the mixture at −50° C. and the mixture stirred for 2 h at −50° C. The mixture was diluted with DCM (50 ml) and saturated sodium bicarbonate solution (50 ml) was added and the organic layer collected using a hydrophobic frit. The aqueous layer was washed with DCM (2×50 ml) and separated by hydrophobic frit. The combined organic phases were concentrated in vacuo. This was purified by chromatography on silica gel, eluting with a gradient of 0-100% ethyl acetate in cyclohexane, followed by 0-20% methanol. The residue was distilled using a Kugelrohr to give the title compound (553 mg) as yellow solid.

1. stirringthe mixture stirred for 2 h at −50° C
2. additionwas added
3. customthe organic layer collected
4. washThe aqueous layer was washed with DCM (2×50 ml)
5. customseparated by hydrophobic frit
6. concentrationThe combined organic phases were concentrated in vacuo
7. customThis was purified by chromatography on silica gel
8. washeluting with a gradient of 0-100% ethyl acetate in cyclohexane
9. distillationThe residue was distilled

ORD record

ord-934227522a7646259d51e3b1fd07704d

Source dataset

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08658635B2