Ethyl oxoacetate → Ethyl 1,3-oxazole-5-carboxylate

Temperature

0 °C

Toluenesulfonylmethyl isocyanide (TosMIc) (12.31 g, 1 wt, 1 eq) is dissolved in DCM (61.6 ml, 5 vols) at 0° C. under N2. In a seperate vessel, ethyl glyoxalate (50 wt % solution in toluene, 20.6 g, 20.0 ml, 1.67 wt) is diluted with DCM (61.6 ml, 5 vols) under N2 and DBU (12.48 g, 12.35 ml, 1.3 eq, 1.01 wt) is added resulting in a purple solution. The second solution is added to the TosMIc solution over 1 hr, maintaining temperature at 0° C., then checked by HPLC for completion after a further 20 mins. The reaction is quenched by slow addition of 2M HCl (10 vols, 123 ml) and the DCM layer separated. The aqueous layer is re-extracted with DCM (5 vols, 61.6 ml), and the combined organics dried over Na2SO4, then evaporated on Buchi, 25° C., 100 mbar to remove DCM and toluene. Distilled at 12 mbar, jacket temperature 105° C., vapour temperature 60-80° C. to afford ethyl oxazole-5-carboxylate as a colourless oil.

1. customresulting in a purple solution
2. customThe reaction is quenched by slow addition of 2M HCl (10 vols, 123 ml)
3. customthe DCM layer separated
4. extractionThe aqueous layer is re-extracted with DCM (5 vols, 61.6 ml)
5. dry with materialthe combined organics dried over Na2SO4
6. customevaporated on Buchi, 25° C., 100 mbar
7. customto remove DCM and toluene
8. distillationDistilled at 12 mbar, jacket temperature 105° C.
9. customtemperature 60-80° C.

ORD record

ord-8b49dfe0b60e46aca55002a150e65d76

Source dataset

uspto-grants-2015_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08993576B2