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20th August 2018 @ 22:02

This reaction was performed by Heath, Ronan, Francis, Nathan, Jonah, Oliver, Daniel, Stuart, Jacky and Erin.

Synthesis of 18-3-1

3-(Trifluoromethyl)phenylacetonitrile (11.4g, 0.0617 mol) was added to ethyl propanoate (5.35 g, 0.0524 mol) and THF (100 mL). Potassium tert-butoxide (17.0 g, 0.152 mol) 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.

A TLC was run in 25:75 EtOAc:hex, and showed that the crude mixture contains some starting material and two coloured spots. This is consistent with the expected keto and enol tautomers.

 

TLC 75:25 hexane:EtOAc

3rd June 2018 @ 22:06

Reaction performed by Heath, Jonah, Ronan, Francis, Stuart, Daniel, Oliver, Jacky, Nathan and Erin!

SGS18-2-1

4-(trifluoromethyl)phenylacetonitrile (10 g, 0.054 mol) was added to ethyl propanoate (5.52 g, 0.055 mol) and THF (100 mL), and stirred until dissolved. Potassium tert-butoxide (12.5 g, 0.112 mol) was added with stirring.  The reaction immediately turned red and warmed to ~40 oC.  The reaction was kept at this temperature and stirred for 7 h.

HCl (80 mL, 1 M) was added to stop the reaction, then DCM (40 mL) was added. The intense red organic layer was collected, and the aqueous layer extracted with DCM (20 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. 

After addition of potassium tert-butoxide

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).

24th November 2017 @ 01:20

 

 

 

SGS 17-5-1

SGS17-5-1 crude.png
SGS17-5-1 crude.mnova
SGS17-5-1 crude.jcamp

N#C/C(C1=CC=C(C(F)(F)F)C=C1)=C(OCC(C)C)/CC

InChI=1S/C16H18F3NO/c1-4-15(21-10-11(2)3)14(9-20)12-5-7-13(8-6-12)16(17,18)19/h5-8,11H,4,10H2,1-3H3/b15-14+

  

SGS 17-6-1

SGS17-6-1 crude.png
SGS17-6-1 crude.mnova
SGS17-6-1 crude.jcamp

NC1=C(C(CC)=NC(N)=N1)C2=CC(C(F)(F)F)=CC=C2

InChI=1S/C13H13F3N4/c1-2-9-10(11(17)20-12(18)19-9)7-4-3-5-8(6-7)13(14,15)16/h3-6H,2H2,1H3,(H4,17,18,19,20)

 

SGS 17-7-1

SGS17-7-1.png
 
SGS17-7-1.jcamp
SGS17-7-1.mnova

N#C/C(C1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1)=C(OCC(C)C)/CC

InChI=1S/C17H17F6NO/c1-4-15(25-9-10(2)3)14(8-24)11-5-12(16(18,19)20)7-13(6-11)17(21,22)23/h5-7,10H,4,9H2,1-3H3/b15-14+


SGS 17-8-1

SGS17-8-1 crude.png
SGS17-8-1 crude.jcamp
SGS17-8-1 crude.mnova

NC1=C(C(CC)=NC(N)=N1)C2=CC=C(C(F)(F)F)C=C2

InChI=1S/C13H13F3N4/c1-2-9-10(11(17)20-12(18)19-9)7-3-5-8(6-4-7)13(14,15)16/h3-6H,2H2,1H3,(H4,17,18,19,20)

Attached Files
23rd November 2017 @ 00:30

 

 

 

  

SGS 17-3-1

SGS17-3-1proton.png
SGS17-3-1proton.jcamp
SGS17-3-1proton.mnova

O=C(CC)C(C#N)C1=CC=C(C(F)(F)F)C=C1

InChI=1S/C12H10F3NO/c1-2-11(17)10(7-16)8-3-5-9(6-4-8)12(13,14)15/h3-6,10H,2H2,1H3


SGS 17-4-1

SGS17-4-1.png
SGS17-4-1.jcamp
SGS17-4-1.mnova

O=C(CC)C(C#N)C1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1

InChI=1S/C13H9F6NO/c1-2-11(21)10(6-20)7-3-8(12(14,15)16)5-9(4-7)13(17,18)19/h3-5,10H,2H2,1H3


SGS 17-5-1

SGS17-5-1.png
SGS17-5-1.jcamp
SGS17-5-1.mnova

N#C/C(C1=CC=C(C(F)(F)F)C=C1)=C(OCC(C)C)/CC

InChI=1S/C16H18F3NO/c1-4-15(21-10-11(2)3)14(9-20)12-5-7-13(8-6-12)16(17,18)19/h5-8,11H,4,10H2,1-3H3/b15-14+

Attached Files