KBS34-2 - Synthesis of methyl quinoline-2-carboxylate (5 g scale)

[KlementineJBS]

Link to HIRAC and original method.

KBS34 - Synthesis of methyl quinoline-2-carboxylate.docx

Previous attempt is #112

Reaction scheme

Outcome

2.9404 g (15.7 mmol, 55%)

[KlementineJBS]

1. Dissolved quinaldic acid (4.9752 g, 28.7 mmol) in methanol (50 mL)
2. Added concentrated sulfuric acid (98%, 1.5 mL)

Cloudy pale reaction mixture turned to a clear amber colour after addition of acid.

3. Left stirring at 75 C from 5 pm

[KlementineJBS]

TLC at 10 am indicated reaction was progressing but perhaps not quite complete. This was confirmed by NMR, which indicated approximately a 1:5 ratio of SM:product (based on integrals).

Eluent is 1% ammonium hydroxide, 9% methanol, 90% DCM

KBS34-2 RM.pdf KBS34-2 RM_1.zip

Left stirring on heat until ~5 pm. TLC looked similar but worked up anyway.

4. Neutralised to pH 10/11 with sodium carbonate solution (sat.)
5. Extracted with chloroform (3 x 50 mL)
6. Dried over mag sulphate and rotovapped

Empty vial: 16.0087 Full vial: 18.9491 Mass: 2.9404 g (15.7 mmol, 55%)

[KlementineJBS]

H NMR

Material confirmed to be product via NMR. Will try further extraction of aqueous to improve yield.

KBS34-2 cr_1.zip KBS34-2 cr.pdf

[KlementineJBS]

Performed another extraction with DCM (3 x 100 mL). Only obtained ~72 mg of product but does appear to be same product.

KBS34-2 2nd extract_1.zip KBS34-2 2nd extract.pdf

[KlementineJBS]

Quinoline pKa is ~9.5 so need to basify more.

[KlementineJBS]

20230728_BS5-3.pdf