2-Fluoro-4-methyl-6-nitrophenol → 2-Amino-6-fluoro-4-methylphenol

Participants

Reaction Steps

2-Fluoro-4-methyl-6-nitrophenol (D51, 3.276 g, 19.14 mmol) was dissolved in ethanol (100 mL). 10% Pd/C (0.323 g, 0.304 mmol) was added and the reaction mixture hydrogenated for ˜18 hr. Catalyst was filtered off and the filtrate evaporated to dryness. TLC showed only a small amount of material had been reduced. Solid was redissolved in 350 mL ethanol, 150 mL of this solution was passed down the H-cube at 1 mL/min with full hydrogen. After ˜2 hr the cartridge had been exhausted. A new cartridge was used and the reaction mixture was left recycling through the instrument for ˜4 hr. ˜30% of nitro compound was still remaining. The reaction mixture was evaporated to dryness. Redissolved in EtOH and passed through the H-cube with a new cartridge to give fully reduced material 2-fluoro-4-methyl-6-aminophenol (907 mg, 6.43 mmol, 33.6% yield) as a brown solid. The remaining nitro compound was passed down the H-cube at 1 mL/min with full hydrogen—still only 58% conversion. Redissolved in EtOH and passed through the H-cube with a new cartridge. Evaporated to dryness redissolved in MeOH and loaded onto an SCX-2 cartridge (50 g) washed with MeOH and eluted with 1M NH3/MeOH, evaporated to dryness to give a brown solid batch 2 (1.319 g, 9.35 mmol, 48.8% yield).

Provenance & Evidence