KBS36-1 - Synthesis of 1-(5-phenylpyridin-2-yl)ethan-1-one

[KlementineJBS]

Link to HIRAC and original method.

KBS36 - Synthesis of 1-(5-phenylpyridin-2-yl)ethan-1-one.docx

Reaction scheme

Need to do under nitrogen!

Outcome

Mass: 337.5 mg, of which 287.6 mg is calculated to be product

Appears to be approximately 85% conversion rate, giving a yield of 83%.

[KlementineJBS]

1. Added the following to a 25 mL 2-neck flask: phenylboronic acid (263 mg, 2.16 mmol, 1.2 equiv.), 2-acetyl-5-bromopyridine (350 mg, 1.75 mmol), potassium carbonate (483 mg, 3.49 mmol, 2 equiv.) and Pd(Ph3)4 (10 mg, 0.008 mmol)

2. Evacuated and backfilled flask x 5

3. Added toluene (10 mL) and water (2 mL)

4. Swapped out to a condenser

5. Heated to 105 C from 1.30 pm

Discovered at 4 pm that reaction had gone dry. Added the same solvents again. TLC indicated no reaction.

[KlementineJBS]

TLC at 10 am indicated reaction was progressing but incomplete. Lots of yellow precipitate was present on the edge of the flask.

TLC'd again at 5 pm. Looked similar. Topped up solvents (1 mL water, 5 mL toluene) and left overnight.

Eluent is 10% ethyl acetate in hexanes

[KlementineJBS]

LRMS

target weight 211.pdf
KBS36-1.pdf
KBS36-1.d.zip

[KlementineJBS]

H NMR

Indicates that product was formed (methyl peak at 2.79) but some starting material remains (methyl peak at 2.70). See literature reference.

KBS36-1 cr.pdf
KBS36-1 cr_1.zip
2-acetyl-5-bromopyridine_1.zip

[KlementineJBS]

Yield and conversion calculations

Empty vial: 15.8813
Full vial: 16.2188
Mass: 337.5 mg, of which 287.6 mg is calculated to be product

Appears to be approximately 85% conversion rate, giving a yield of 83%.

Bromination percentage calculations.xlsx

[KlementineJBS]

LRMS

Peak at 220.11 [M+Na]+ confirms that fractions 10+ are probably product.

KBS36-1 F10+.pdf
KBS36-1 F10+.d.zip

[KlementineJBS]

H NMR

NMR of column fractions indicates that fractions 7-9 and 10+ are product.
(SM peak at 2.68, product at 2.78)

KBS36-1 column.pdf
KBS36-1 F1-2_1.zip
KBS36-1 F3-6_1.zip
KBS36-1 F7-9_1.zip
KBS36-1 F10+_1.zip

[KlementineJBS]

IR

KBS36-1 all peaks.pdf
KBS36-1.pdf

KBS34,36,37.zip