Ammonia → HCID 67207384, compound

Paraformaldehyde (0.35 g) was added in portions to a mixture of phenol (487.8 mg, 3.33 mmol), triethylamine (1.3 mL, 9.33 mmol), and anhydrous MgCl2 (0.98 g, 10.3 mmol) in acetonitrile (30 mL). The mixture was refluxed for 48 h, cooled to room temperature, acidified with aqueous 3 N HCl solution, and extracted with ether. The ether layer was washed with water, and brine, and dried (MgSO4). Removal of solvent yielded a crude material which was purified by column chromatography (SiO2) to yield 3-chloro-5-fluoro-2-hydroxybenzaldehyde. To this aldehyde (0.25 mmol) in at room temperature was added 3 mL of NH3 (2.0 M solution in EtOH) solution and the solution was stirred overnite (upon addition of NH3 in ethanol, the solution changed to yellow). TosMIC (0.30 mmol equiv) and piperazine (0.38 mmol) were then added directly to the solution at room temperature in solid form. The solution were stirred at room temperature for 3 h until completion confirmed by TLC monitor. The solvent was evaporated mostly under reduced pressure and the crude was purified by column chromatography using 1:1 Hexanes and Ethyl acetate mixtures to afford the desired product as a light yellow solid. Yield=65%. 1H NMR (MeOH-d4): 6.95-6.99 (m, 1H), 7.29-7.33 (m 1H), 7.61 (s, 1H), 7.84 (s, 1H).

1. stirringThe solution were stirred at room temperature for 3 h until completion
2. customThe solvent was evaporated mostly under reduced pressure
3. customthe crude was purified by column chromatography

ORD record

ord-063f23e0a05745ae95e6518f67d80762

Source dataset

uspto-grants-2014_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08722720B2