Sulfuric Acid → HCID 86707803, compound

Participants

Reaction Conditions

Reaction Steps

(4aS,5R,7aS)-7a-(2-Fluorophenyl)-5-methyl-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-2-amine* (1.0 g, 3.75 mmol) was dissolved in trifluoroacetic acid (3.5 mL, 45.4 mmol). Sulfuric acid (1.2 mL, 22 mmol) was carefully added dropwise, keeping temperature below 30° C. N-Bromosuccinimide (0.74 g, 4.13 mmol) was added portionwise and the reaction was warmed to 55-60° C. After 30 minutes, the reaction was cooled to room temperature and added dropwise to a cooled solution of sodium hydroxide (3.00 g, 75.1 mmol) in water (25 mL). The solution of reaction mixture in sodium hydroxide solution was extracted with EtOAc (×2), checking the pH to ensure the TFA/H2SO4 had all been neutralised. The organic layer was washed with brine and concentrated to leave a brown solid. The solid was recrystalised from IPA (10 mL): heating to 50° C. for 15 minutes on the rotavap under slight vacuum. The suspension was cooled to room temperature, filtered and washed with IPA (2 mL) and heptane (10 mL). The solid was dried overnight to give the title compound (1.30 g). 1H NMR (400 MHz, CDCl3) δ ppm: 7.55 (dd, J=7.2, 2.7 Hz, 1H), 7.36 (ddd, J=8.7, 4.2, 2.5 Hz, 1H), 6.94 (dd, J=11.6, 8.6 Hz, 1H), 4.55 (dd, J=8.8, 1.3 Hz, 1H), 4.35 (q, J=1.0 Hz, 1H), 3.77 (dd, J=8.8, 2.3 Hz, 1H), 3.07 (dd, J=13.4, 3.5 Hz, 1H), 2.71 (dd, J=13.3, 3.9 Hz, 1H), 2.44-2.53 (m, 1H), 1.37 (d, J=6.1 Hz, 3H)

Provenance & Evidence