Formaldehyde → HCID 69452543, compound

Participants

Reaction Steps

A mixture of acetophenone (414 mg, 3.45 mmol), 4-(2,5-dimethyl-2H-pyrazol-3-yl)piperidine.TFA salt (prepared as described for 4-(2-ethyl-5-methyl-2H-pyrazol-3-yl)piperidine in Example 3, Steps 1 and 2) (1.1 g, 3.80 mmol) and paraformaldehyde (120 mg, 4 mmol) in EtOH (2 mL) and conc. HCl (5 μL) was heated at reflux for 14 h and then cooled to RT and concentrated under reduced pressure. The residue was taken up in EtOH (10 mL), NaBH4 (260 mg, 6.9 mmol) added and the mixture stirred at RT for 15 min, then more NaBH4 (260 mg, 6.9 mmol) was added. After stirring for a further 5 min, NH4Cl solution (5 mL) was added and the organic solvents removed under reduced pressure. The aqueous was extracted with CH2Cl2 (3×50 mL). The organic extracts were concentrated under reduced pressure whilst dry loading onto MgSO4 and purified by column chromatography on silica eluting with 8% MeOH/CH2Cl2 to yield the desired alcohol (334 mg, 28%). 1H NMR (CDCl3, 400 MHz) δ 7.43–7.32 (4H, m), 7.29–7.22 (1H, m), 5.81 (1H, s), 4.95 (1H, dd, J=7.0, 4.4 Hz), 3.74 (3H, s), 3.21 (1H, d, J=12.3 Hz), 3.14 (1H, d, J=11.9 Hz), 2.75–2.67 (1H, m), 2.63–2.52 (2H, m), 2.24–2.15 (1H, m), 2.22 (3H, s), 2.06–1.65 (7H, m). MS (ES+) C19H27N3O requires: 313, found: 314 (M+H+, 100%).

Provenance & Evidence