Acetic Acid → HCID 67293310, compound

Participants

Reaction Steps

6-Nitro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole-3-carbaldehyde (1.72 g, 5.35 mmol, Preparation #N.1) was added to a solution of 2-methyl-2-butene (2.0 M in THF, 26.8 mL, 53.5 mmol) and t-BuOH (48.2 mL) under N2. A solution of sodium dihydrogen phosphate (3.35 g, 27.9 mmol) and sodium chlorite (1.50 g, 16.6 mmol) in water (16.1 mL) was added and the mixture was stirred at rt for about 3 h. The mixture was concentrated under reduced pressure. DCM (50 mL) and aqueous 1 N HCl (20 mL) were added and the layers separated. The aqueous layer was extracted with DCM (15 mL). The combined organic layers were washed with brine (10 mL), dried over Na2CO3, filtered, and concentrated under vacuum. The solid was dissolved in a mixture of THF (64.3 mL) and MeOH (16.1 mL). (Trimethylsilyl)diazomethane (2 M in Et2O, 4.01 mL, 8.03 mmol) was added drop-wise. After about 2 h, AcOH (1 mL) was added and the mixture was stirred for about 14 h. The mixture was concentrated under reduced pressure. DCM (100 mL) was added and the mixture was washed with an aqueous solution of saturated NaHCO3 (25 mL) and the layers separated. The organic layer was washed with brine (10 mL), dried over Na2CO3, filtered and concentrated in vacuo. The residue was purified by column chromatography (80 g silica gel) eluting with 10 to 20% EtOAc/heptane to provide methyl 6-nitro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole-3-carboxylate (1.66 g, 88%): LC/MS (Table 2, Method c) Rt=2.99 min.; MS m/z: 352 (M+H)+, 369 (M+H2O)+.

Provenance & Evidence