All Notebooks | Help | Support | About
12th May 2014 @ 01:42

Reaction completed successfully, with quantitative conversion and 90 % recovered yield.

Carrying pure material from Resynthesis of methyl 6-chloro-2-pyrazinecarboxylate (TM 5-3) forward on a 2 gram test scale. If successful, this will finally give access to key starting material 6-chloropyrazine-2-carboxylic acid, needed for all series 4 amides. A modified hydrolysis reaction taken from DOI: 10.1039/C2NJ40791D is to be used, with THF as the solvent (unlike Synthesis of 6-chloropyrazine-2-carboxylic acid (TM 10-1), where ethanol was used and found to substitute the chloride to give an ethoxypyrazine product).








 

10-2 scheme

TM 5-3 (2.00 g, 11.6 mmol) was dissolved in THF (60 mL), and NaOH (2M, 10 mL) added. The reaction mixture was stirred at room temperature for one hour, and slowly changed from a yellow solution to a milky white suspension. The mixture was  then acidified with HCl (1M, ~20 mL), to pH ~3. Volatiles were removed under vacuum to give brown flakes, which was dissolved in acetone (100 mL), aided by mechanical stirring. Solution dried over anhydrous Na2SO4, then acetone removed under vacuum to give TM 10-2 as brown flakes. Crude yield: 1.66 g, 10.5 mmol, 90.5 % (after drying on highvac).

Crude NMR (1H, DMSO, 400 MHz):

TM 10-2 crude 1H DMSO 400 MHz.pdf
TM 10-2 crude DMSO.zip

Commercially obtained 6-chloropyrazine-2-carboxylic acid NMR (1H, DMSO, 400 MHz):

6-chloropyrazine-2-carboxylic acid 1H DMSO 400 MHz.pdf
6-chloropyrazine-2-carboxylic acid.zip

The reaction appears to have been successful, but with around 10 % by remaining m-chlorobenzoic products (interestingly, the commercially obtained standard has the same contamination, but at around 2 %). The ester appears to have been hydrolysed quantitatively.

HIRAC:

HIRAC.pdf
Linked Posts
Attached Files
scheme.cdx
scheme.png
HIRAC.pdf
6-chloropyrazine-2-carboxylic acid 1H DMSO 400 MHz.pdf
TM 10-2 crude 1H DMSO 400 MHz.pdf
6-chloropyrazine-2-carboxylic acid.zip
TM 10-2 crude DMSO.zip
Comments