Pyrazole → HCID 11568000, compound

Participants

Reaction Steps

A solution of 6.2 g (10.1 mmol) 3-6 in 200 ml 1:1 EtOAc/EtOH was evacuated under reduced pressure and purged three times with N2 before 200 mg of 10% Pd/C was added. The solution was then evacuated and purged twice with N2, then three times with H2, and stirred at room temperature overnight under a balloon of H2. The mixture was purged with nitrogen, filtered through a pad of celite, and concentrated to give the phenolic pryazole as an amber gum. LC-MS: rt=2.8 min, m/z=441 (M−THP+1). Without further purification, 4.45 g (8.5 mmol) of the phenolic pyrazole was combined with 200 ml of THF, 3.34 g (12.7 mmol) triphenylphosphine and 2.67 ml (17 mmol) DEAD. After stirring for 1 h at room temperature, the solution was dumped into a separatory funnel with 150 ml of EtOAc and successively washed with 50 ml portions of 10% aqueous KHSO4, saturated aqueous NaHCO3, and brine. The organic layer was dried over MgSO4, concentrated, and purified by silica gel chromatography with EtOAc/hexanes to give the THP protected tricycle as colorless gum. LC-MS: rt=3.2 min, m/z=423 (M−THP+1). To a solution of 950 mg (1.9 mmol) of the THP protected tricycle in 100 ml of MeOH was added 1 g (5.3 mmol) of p-toluenesulfonic acid monohydrate, the resulting mixture was stirred at room temperature for 1 h, and concentrated. The residue was purified by reverse phase preparative HPLC using two stacked Waters 40×100 mm PrepPak® cartridges with an 85-5% H2O/CH3CN (0.1% trifluoroacetic acid) 40 minute gradient to give 3-7 as a white solid. Data for 3-7: LC-MS: rt=2.6 min, m/z=423 (M+1).

Provenance & Evidence