HCID 3811668, compound → HCID 178441047, compound

Participants

Reaction Steps

To a solution of 1-(1-pyrrolidinomethyl)-pyrazole (Katrikzky, A. R.; Rewcastle, G. W.; Fan, W-Q., J. Org. Chem., 1988, 53, 5688) (3.32 g, 0.022 mole) in THF (75 mL) at -70° C. is added 1.6M n-butyllithium (14 mL) over a 20-minute period. After stirring at that temperature 1.5 hours a solution of N-methoxy-N-methyl-[3,5-di-tert-butyl-4[(2-methoxyethoxy) methoxy] -benzamide (Example 6) (7.62 g, 0.02 mole) in THF (75 mL) is added over a 30-minute period. The reaction mixture is allowed in warm to room temperature, treated with ice-cold 2N HCl (200 mL) and concentrated to remove the THF. The concentrated mixture is extracted with CH2Cl2. The extracts are washed with saturated NaHCO3 and brine, dried with Na2SO4 and evaporated. The residue is purified by flash chromatography (0-30% EtOAc/CH2Cl2) on silica gel to give 6.25 g of an oil. This product is deprotected by allowing to stand in 5% (w/v) HCl/MeOH (150 mL) for 2 days. The acid solution is evaporated and the residue is taken up in Et2O. The resulting solution is washed with saturated NaHCO3 and brine, and dried with Na2SO4. The ethereal solution is concentrated causing the precipitation of 3.62 g (75% of a white solid, [3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]-1H-pyrazol-3-yl methanone, mp 216°-219° C. 1H NMR (DMSO-d6) δ 1.42 (s, 18H, tert-butyl), 6.84 (m, 1H, OH), 8.19 (s, 2H, phenyl aromatics); pyrazole aromatics and NH appear as several poorly defined signals because of tautomerization at 7.6-7.9, 13.4, 13.9; IR (KBr) 1430, 1592, 1643 cm-1 ; MS (DEI) m/e 301 (M+ +1), 300 (M+), 95.

Provenance & Evidence