Acetic Acid → HCID 4025213, compound

Participants

Reaction Steps

NaBH4 (1.50 g, 38.88 mmol, 1.2 equiv.) was slowly added over 20 minutes to a solution of acetic acid (glacial, 11.13 mL, 194.41 mmol, 6 equiv.) in anhydrous THF (50 mL) at 20° C. under a nitrogen blanket with stirring at 200 RPM. After aging for another 20 minutes, pre-dried molecular sieves (3A, 45 g) and additional anhydrous THF (20 mL) were added to the reaction mixture and the stirring rate was increased to 350 RPM. Ten minutes after addition of the sieves, 1-phenylpiperazine (4, 5.00 mL, 32.40 mmol, 1 eq.) and 3-pyridinecarboxaldehyde (2, 3.74 mL, 38.88 mmol, 1.2 equiv.) were added, and the mixture aged for another 30 minutes, at which point the reaction was 100% complete, as determined by monitoring the disappearance of 4 with HPLC. The molecular sieves were removed by filtration. The filtrate containing the product was quenched into brine and the pH adjusted to 7.5 to 8. The organic layer containing the product was separated and the aqueous layer discarded. The organic layer was then concentrated to dryness and the solids dissolved in hot hexanes. The desired product was then crystallized by slow cooling to 5–10° C. The resulting crystals were vacuum filtered while cold and washed with cold hexane (50 mL×2). The product was then dried under vacuum at 45° C. and 75 mm Hg pressure. The isolated yield of compound 6 (HPLC area 99.3%, mp 70.5–72.0° C.) was 90.7%.

Provenance & Evidence