반응 #155567

반응 방정식

NBS

NaOH

N-((4aS*,5R*,7aS*)-7a-(2,4-Difluorophenyl)-5-methyl-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-2-yl)benzamide

TFA

sulfuric acid

→

desired compound

N-((4aS*,5R*,7aS*)-7a-(5-Bromo-2,4-difluorophenyl)-5-methyl-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-2-yl)benzamide

반응 조건

후처리

1. 1
   온도The reaction mixture was cooled to room temperature
2. 2
   추출extracted with EtOAc (×3)
3. 3
   기타The combined organics were dried
4. 4
   농축concentrated in vacuo
5. 5
   기타The residue was purified by column chromatography
6. 6
   세척eluting with 0-30% EtOAc in n-hexane

실험 절차

N-((4aS*,5R*,7aS*)-7a-(2,4-Difluorophenyl)-5-methyl-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-2-yl)benzamide (95 mg, 0.24 mmol) was dissolved in TFA (218 μL, 2.93 mmol) and sulfuric acid (78.2 μl, 1.47 mmol). NBS (39 mg, 0.22 mmol) was added and the reaction was stirred at 60° C. for 1 hour. The reaction mixture was cooled to room temperature, neutralized with 2N NaOH and extracted with EtOAc (×3). The combined organics were dried and concentrated in vacuo. The residue was purified by column chromatography, eluting with 0-30% EtOAc in n-hexane to give the desired compound. (78 mg). 1H NMR (400 MHz, CDCl3) δ ppm: 8.05-8.10 (m, 2H), 7.52-7.62 (m, 2H), 7.44-7.51 (m, 2H), 6.95-7.04 (m, 1H), 4.46-4.53 (m, 2H), 3.95 (dd, J=2.45, 9.41 Hz, 1H), 3.17 (dd, J=3.42, 13.45 Hz, 1H), 2.77-2.83 (m, 1H), 2.70-2.77 (m, 1H), 1.37-1.46 (m, 3H).

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