Réaction #155560

Équation de réaction

NaOH

sulfuric acid

(4aS,5S,7aS)-7a-(2,4-Difluorophenyl)-5-(fluoromethyl)-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-2-amine

NBS

→

title compound

(4aS,5S,7aS)-7a-(5-bromo-2,4-difluorophenyl)-5-(fluoromethyl)-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-2-amine

Solvants

TFA

Conditions de réaction

Traitement

1. 1
   ExtractionThe mixture was then extracted with EtOAc (×3)
2. 2
   SéchageThe combined organics were dried (MgSO4)
3. 3
   Concentrationconcentrated in vacuo
4. 4
   AutreThe residue was purified
5. 5
   Lavageeluting with 20-80% EtOAc in n-hexane

Mode opératoire

(4aS,5S,7aS)-7a-(2,4-Difluorophenyl)-5-(fluoromethyl)-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-2-amine (700 mg, 2.32 mmol) was dissolved in TFA (2.1 mL) and sulfuric acid (864 μL, 16.2 mmol). NBS (453 mg, 2.55 mmol) was added and the reaction was stirred at 60° C. for 45 minutes. The reaction was cooled to room temperature and basified with 2N NaOH. The mixture was then extracted with EtOAc (×3). The combined organics were dried (MgSO4) and concentrated in vacuo. The residue was purified using column chromatography, eluting with 20-80% EtOAc in n-hexane to give the title compound. (620 mg). 1H NMR (400 MHz, CDCl3) δ ppm: 7.67 (t, J=8.13 Hz, 1H), 6.94 (dd, J=8.01, 11.55 Hz, 1H), 4.65 (d, J=4.16 Hz, 1H), 4.47-4.57 (m, 3H), 3.84-3.98 (m, 1H), 3.01-3.20 (m, 2H), 2.77-2.91 (m, J=13.40 Hz, 1H).

Source