Acetic Acid → HCID 57791794, compound

Participants

Reaction Conditions

Reaction Steps

(S)-4-(1-methoxypropan-2-yloxy)pyridine (91) (15 g, 89.71 mmol) and Platinum(IV) oxide in MeOH (50 mL) were stirred under an atmosphere of hydrogen at 50 bar and 80° C. for 16 hours. Analysis indicated no reaction, so 20 ml of acetic acid was added and the temperature increased to 100° C. and pressure increased to 80 bar for another 18 hrs, Still very little reaction observed. An aliquot of 5% Rhodium on alumina was added and the mixture heated overnight at 100° C., 80 bar. GCMS-2 indicated more product formation so reaction put back on at 100° C. again as the impurity peak doesn't seem to be increasing. GCMS-3 indicated more product formation so reaction put back on at 100° C. again for 48 hours as the impurity peak doesn't seem to be increasing. GCMS-4 indicated more product formation so reaction put back on at 100° C. again for 48 hours as the impurity peak doesn't seem to be increasing. GCMS-5 showed just a trace of SM with the main peak being product with the impurity slightly increased. The reaction was filtered and the solvent evaporated, the reaction was quenched with 2M NaOH (75 mL), extracted with EtOAc (3×75 mL), the organic layer was dried over MgSO4, filtered and evaporated to afford a yellow liquid. The crude product was purified by distillation at 0.89 mBar, collecting fractions that distilled at 70° C. to afford the desired compound as a colourless liquid (2.500 g, 16.08% yield); 1H NMR (400.132 MHz, CDCl3) δ 1.14 (3H, d), 1.47-1.37 (2H, m), 1.94-1.83 (2H, m), 2.62-2.56 (2H, m), 3.10-3.06 (2H, m), 3.30-3.26 (1H, m), 3.40-3.36 (4H, m), 3.50-3.44 (1H, m), 3.75-3.66 (1H, m); NH missing.

Provenance & Evidence