Hydrochloric Acid → HCID 67468652, compound

Participants

Reaction Conditions

Reaction Steps

To tert-butyl (3Z)-3-(ethoxymethylene)-7-fluoro-4-oxo-spiro[chromane-2,4′-piperidine]-1′-carboxylate (2.6 g, 5.9 mmol) was added hydrochloric acid (22.3 mL, 89.1 mmol) (4 M in dioxane). The reaction mixture was allowed to stir at 25° C. for 2 hours. Solvent was removed under vacuum, and the obtained solid was dissolved in EtOH (3×25 mL) and the solvent was evaporated to dryness. The resulting beige-white solid was fully dissolved in ethanol (21 mL) at 25° C. prior to the addition of tert-butyl N-amino-N-methyl-carbamate (1.0 g, 7.1 mmol). The solution was allowed to stir at 25° C. overnight. To the thick beige-white slurry that formed was added hydrochloric acid, 4 M in dioxane (7.4 mL, 29.7 mmol). The mixture was heated at 60° C. to yield a clear yellow solution. After 1 hour at 60° C., a thick beige-white slurry developed. The slurry was allowed to slowly cool to 25° C. over 1 hour, and solids were collected by vacuum filtration. The cake was rinsed with a 10% solution of ethanol in hexanes (2×). Residual solvent was further removed under reduced pressure providing 7-fluoro-1-methyl-spiro[chromeno[4,3-c]pyrazole-4,4′-piperidine] dihydrochloride (1.4 g, 67%) as a light tan solid. ESI-MS m/z calc. 273.1, found 274.3 (M+1)+; Retention time: 1.59 minutes (3 min run). 1H NMR (400 MHz, MeOD) δ 7.80 (dd, J=8.7, 6.1 Hz, 1H), 7.45 (d, J=1.7 Hz, 1H), 7.00 (dd, J=9.8, 2.6 Hz, 1H), 6.91 (td, J=8.6, 2.6 Hz, 1H), 4.14 (s, 3H), 3.53-3.42 (m, 2H), 3.41-3.33 (m, 2H), 2.29 (d, J=13.9 Hz, 2H), 2.23-2.11 (m, 2H).

Provenance & Evidence