Hydrogen Peroxide → HCID 58304250, Verbindung

HRID 1626087Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1626087
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([F:18])=[C:6]([C@:8]2([CH3:17])[C:13]([F:15])([F:14])[CH2:12][O:11][C:10]([NH2:16])=[N:9]2)[CH:7]=1.[I-:19].[NH4+].OO>C(O)(=O)C>[NH2:1][C:2]1[C:3]([I:19])=[CH:4][C:5]([F:18])=[C:6]([C@:8]2([CH3:17])[C:13]([F:14])([F:15])[CH2:12][O:11][C:10]([NH2:16])=[N:9]2)[CH:7]=1

Komponenten

5

Edukt 3

HCID 784Hydrogen Peroxide2×HCID 25487Ammonium iodide2×HCID 58304207(R)-4-(5-amino-2-fluoro-phenyl)-5,5-difluoro-4-methyl-5,6-dihydro-4H-[1,3]oxazin-2-ylamine

Produkt 1

HCID 58304250HCID 58304250, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 176Acetic AcidLösungsmittel

Versuchsvorschrift

A solution of (R)-4-(5-amino-2-fluoro-phenyl)-5,5-difluoro-4-methyl-5,6-dihydro-4H-[1,3]oxazin-2-ylamine (intermediate A8.5) (500 mg, 1.9 mmol) and ammonium iodide (308 mg, 2.1 mmol) in acetic acid (9.6 ml) was treated at room temperature with an aqueous solution of hydrogen peroxide (35%, 0.19 ml, 2.1 mmol). After stirring overnight 50% of the starting material was left. Another equivalent of ammonium iodide and hydrogen peroxide was added and stirring continued at room temperature overnight. For the workup, the reaction mixture was filtered, the filtrate treated with sodium thiosulphate, then extracted with ethyl acetate (3×). The combined organic layers were washed with a saturated solution of sodium hydrogen carbonate, then dried over sodium sulphate and evaporated at reduced pressure. In order to eliminate residual acetic acid, the crude product was dissolved in dichloromethane and extracted again with a saturated solution of sodium hydrogen carbonate. The crude product was purified by chromatography on an Isolute flash NH2 column using a gradient of heptane/ethyl acetate=100/0 to 0/100 as the eluent. The (R)-4-(5-amino-2-fluoro-4-iodo-phenyl)-5,5-difluoro-4-methyl-5,6-dihydro-4H-[1,3]oxazin-2-ylamine was obtained as a yellow solid (415 mg, 56% of theory). MS (ISP): m/z=386.0 [M+H]+.

Aufarbeitung

  1. waitwas left
  2. filtrationFor the workup, the reaction mixture was filtered
  3. additionthe filtrate treated with sodium thiosulphate
  4. extractionextracted with ethyl acetate (3×)
  5. washThe combined organic layers were washed with a saturated solution of sodium hydrogen carbonate
  6. dry with materialdried over sodium sulphate
  7. customevaporated at reduced pressure
  8. dissolutionthe crude product was dissolved in dichloromethane
  9. extractionextracted again with a saturated solution of sodium hydrogen carbonate
  10. customThe crude product was purified by chromatography on an Isolute flash NH2 column

Quellen und Nachweise

ORD-Eintrag
ord-8011197020b5454fa1483bb5a3e8c7c0
Quelldatensatz
uspto-grants-2014_07
Patentnummer
US08785436B2

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