Methyl iodide → methyl (2-methyl-3-oxo-2,3,4,5-tetrahydro-1H-2-benzazepin-4-yl)carbamate

HRID 1986532

Reaktionsgleichung

Reaktionsgleichung von HRID 1986532
[O:1]=[C:2]1[CH:8]([NH:9][C:10](=[O:13])[O:11][CH3:12])[CH2:7][C:6]2[CH:14]=[CH:15][CH:16]=[CH:17][C:5]=2[CH2:4][NH:3]1.[H-].[Na+].[CH3:20]I.[Cl-].[NH4+]>C1COCC1.CN(C=O)C>[CH3:20][N:3]1[C:2](=[O:1])[CH:8]([NH:9][C:10](=[O:13])[O:11][CH3:12])[CH2:7][C:6]2[CH:14]=[CH:15][CH:16]=[CH:17][C:5]=2[CH2:4]1

Komponenten

7

Edukt 4

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 57722312methyl (3-oxo-2,3,4,5-tetrahydro-1-H-2-benzazepin-4-yl)carbamate

Produkt 1

HCID 57722308methyl (2-methyl-3-oxo-2,3,4,5-tetrahydro-1H-2-benzazepin-4-yl)carbamateAusbeute 44 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 8028TetrahydrofuranLösungsmittel2×

Versuchsvorschrift

A solution of 176 mg (0.75 mmol) of product 1 (methyl (3-oxo-2,3,4,5-tetrahydro-1-H-2-benzazepin-4-yl)carbamate, which can be prepared according to WO 02/057257 and the content of the description of which is incorporated herein by reference), dissolved in a mixture of 2 ml of dry THF and 2 ml of dry DMF is added dropwise at room temperature to a suspension of 36 mg (0.9 mmol) of 60% NaH dispersed in oil, suspended in 2 ml of anhydrous THF, under an inert atmosphere. At the end of the addition, 159 mg (1.5 eq.) of methyl iodide are added. The reaction mixture is then stirred at room temperature for 2 hours, and 10 ml of saturated ammonium chloride solution are then added, while cooling the reaction medium in an ice bath. The mixture is extracted with 3×10 ml of ethyl acetate. The organic phases are combined, washed with 2×10 ml of saturated NaCl solution, dried over magnesium sulfate and evaporated to dryness under reduced pressure. The oily residue obtained is chromatographed on silica gel, eluting with a 90/10 dichloromethane/methanol mixture. 82 mg (44%) of the expected product 2 are obtained in the form of an oil.

Aufarbeitung

  1. additiondispersed in oil
  2. additionare added
  3. temperaturewhile cooling the reaction medium in an ice bath
  4. extractionThe mixture is extracted with 3×10 ml of ethyl acetate
  5. washwashed with 2×10 ml of saturated NaCl solution
  6. dry with materialdried over magnesium sulfate
  7. customevaporated to dryness under reduced pressure
  8. customThe oily residue obtained
  9. customis chromatographed on silica gel
  10. washeluting with a 90/10 dichloromethane/methanol mixture

Quellen und Nachweise

ORD-Eintrag
ord-c4d7c78ce0714674b1e39d042146675a
Quelldatensatz
uspto-grants-2009_06
Patentnummer
US07550453B2

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