Chemical Properties
Dark yellow Solid
Uses
5-Fluoroisatoic Anhydride is a versatile pharmaceutical intermediate used in the preparation of insulin secretagogues, HCV polymerase inhibitors, anxiolytic agents and other bioactive compounds.
Preparation
5-Fluoroisatonic anhydride is prepared from 5-fluoro indole (9d) by stirring in a 4:1 mixture of DMF/H2O for 16 h at room temperature.
1 H NMR (DMSO-d6): δ11.19 (s, br., 1H), 7.36 (dd, J = 8.4, 2.6 Hz, 1H), 6.87 (dt, J = 8.4, 2.2 Hz, 1H), 6.74 (dd, J = 9.3, 2.2 Hz, 1H).
Synthesis
Preparation of compound 1: Synthesis of 5-fluoroisocyanic anhydride. In a 250 mL three-necked flask assembled with a magnetic stir bar and condenser, acetic anhydride (90.0 mL), 5-fluoroindigo (20.62 g, 0.125 mol, 1.00 equiv.) and acetic acid (90 mL) were added sequentially. The reaction system was placed in a water bath and heated to 85 °C. Subsequently, chromium(VI) oxide (20.36 g, 0.204 mol, 1.63 eq.) was added in batches (~0.5 g per batch) to the red solution over 40 minutes. After addition, the reaction mixture was continued to be stirred for 15 minutes and subsequently cooled to 10 °C in an ice bath. The resulting solid product was separated by filtration and washed with 400 mL of water to remove most of the green impurities. The resulting solid was dissolved in 300 mL of a 2:1 (v/v) acetic acid/water mixture, filtered again, and dried overnight in a vacuum oven at 50 °C to afford 5-fluoroisocyanic anhydride as a bright yellow solid (14.45 g, 64% yield).
References
[1] Catalysis Science and Technology, 2015, vol. 5, # 10, p. 4830 - 4838
[2] Angewandte Chemie, 1980, vol. 92, # 3, p. 196 - 197
[3] Patent: US5863944, 1999, A
[4] Journal of the Chemical Society, 1957, p. 2916,2917
[5] Journal of medicinal chemistry, 1971, vol. 14, # 12, p. 1233 - 1235
