Sulfuric Acid → 5-Amino-2-butyl-6-fluoro-1-indanone

Participants

Reaction Steps

A solution of the product mixture from step 4 (19.5 g, approx. 60.7 mmol) in CH2Cl2 (10 mL) was cooled in an ice bath and treated with ice-cold, conc. H2SO4 (300 mL). The resulting mixture was removed from the cooling bath and stirred at room temperature for 18 hours. The mixture was cautiously added to an ice-cold mixture of CH2Cl2 (300 mL) and chopped ice (1 L). Excess acid was neutralized by portionwise addition of saturated Na2CO3 solution (approx. 1 L) followed by solid Na2CO3 (approx. 500 g). Additional water and CH2Cl2 were occasionally added to dissolve the red/purple solids that formed during the neutralization. When the pH was neutral, the organic phase was separated and the aqueous portion was extracted with more CH2Cl2. The combined organics were washed with brine, dried over MgSO4, filtered, and concentrated under vacuum. The residual dark red oil was purified by flash chromatography on a Biotage 75 L KP-Sil column, eluting with 4:1 hexanes-EtOAc. The product containing fractions were combined and evaporated under vacuum to provide 5-amino-2-butyl-6-fluoro-1-indanone (5.5 g, 37%) as a yellow solid.

Provenance & Evidence