Nitric Acid → HCID 71112643, compound

Participants

Reaction Steps

A dispersion of (S)-5,5-difluoro-4-fluoromethyl-4-(2-fluoro-phenyl)-5,6-dihydro-4H-[1,3]oxazin-2-ylamine (intermediate F6.1) (32.5 mg, 124 μmol) in sulfuric acid (1.01 g, 554 μl, 9.92 mmol) was cooled to 0° C. and stirring was continued until a complete solution was obtained. At 0° C. fuming nitric acid (12.1 mg, 8.68 μl, 174 μmol) was added in one portion and stifling continued for 2 hours. For the workup, the solution was added dropwise to a mixture of crushed ice and water. With an aqueous solution of sodium hydroxide (6 M) the pH was adjusted to 7-8. The aqueous layer was extracted three times with ethyl acetate, thereafter the combined organic layers were washed with brine, then dried over sodium sulphate and evaporated at reduced pressure. The (S)-5,5-difluoro-4-fluoromethyl-4-(2-fluoro-5-nitro-phenyl)-5,6-dihydro-4H-[1,3]oxazin-2-ylamine (39 mg, quantitative yield) was obtained as a light yellow solid and was engaged in the following step without further purification. MS (ISP): m/z=308.3 [M+H]+.

Provenance & Evidence