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28th May 2018 @ 21:40

Reaction performed by Stuart, Heath and Francis (contributions by Jonah, Ronan, Nathan, Jacky, Daniel, Oliver and Erin) 

Synthesis of SGS18-1

This is a repeat of SGS 10-2 to verify synthesis and yield of Daraprim.

 (4-chloropenyl)acetonitrile (11.426 g, 75 mmol) was added to ethyl propanoate (7.698 g, 75 mmol) and THF (50 mL). Potassium tert-butoxide (24 g, 214 mmol) was added with stirring. The reaction mixture immediately turned red and warmed. The reaction was then placed in a water bath and the temperature maintained at 40°C with stirring for 7 h. The potassium tert-butoxide dissolved after 30 min of stirring.

HCl (80 mL, 1 M) was added to stop the reaction, then DCM (60 mL) was added. The intense red organic layer was collected, and the aqueous layer extracted with DCM (30 mL x 2). The organic layer was dried over sodium sulfate and then filtered.

TLCs were run in 10:90 EtOAc:hex and 25:75 EtOAc:hex, and both showed that the crude mixture contains some starting material and two coloured spots.  This is consistent with the expected keto and enol tautomers. 

 

TLC 10:90 EtOAc:hex

TLC 10:90 EtOAc:hex. Rf values of major spots are 0.1 and 0.52 (of darker and lighter respectively).

TLC 25:75 EtOAc:hex

TLC 25:75 EtOAc:hex. Rf values of the largest spots are 0.3 and 0.74 (darker and lighter respectively).