Sulfuric Acid → 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

HRID 68385Notes

Reaction equation

HRID 68385 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C@:9]12[CH2:17][O:16][C@H:15]([CH3:18])[C@H:14]1[CH2:13][S:12][C:11]([NH:19][C:20](=[O:27])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)=[N:10]2.C(O)(C(F)(F)F)=O.S(=O)(=O)(O)O.C1C(=O)N([Br:47])C(=O)C1.[OH-].[Na+]>>[Br:47][C:5]1[C:6]([F:8])=[CH:7][C:2]([F:1])=[C:3]([C@:9]23[CH2:17][O:16][C@H:15]([CH3:18])[C@H:14]2[CH2:13][S:12][C:11]([NH:19][C:20](=[O:27])[C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)=[N:10]3)[CH:4]=1

Participants

6

Reactant 5

HCID 1118Sulfuric AcidHCID 6422Trifluoroacetic acidHCID 14798Sodium HydroxideHCID 67184N-bromobutanimideHCID 86707823N-((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

Product 1

HCID 86707824N-((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

Conditions

Temperature
60 °C

Procedure

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).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. extractionextracted with EtOAc (×3)
  3. customThe combined organics were dried
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by column chromatography
  6. washeluting with 0-30% EtOAc in n-hexane

Sources & evidence

ORD record
ord-9d12b066dcc74a4780365ccf63d9b2b8
Source dataset
uspto-grants-2014_09
Patent number
US08822455B2

Reaction notes

Loading…