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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 68385
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 68385
[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
KomponentenReaktionsbedingungenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

6

Edukt 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

Produkt 1

HCID 86707824
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

Reaktionsbedingungen

Temperatur
60 °C

Versuchsvorschrift

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).

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-9d12b066dcc74a4780365ccf63d9b2b8
Quelldatensatz
uspto-grants-2014_09
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08822455B2

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