Reaktion #66839

Reaktionsgleichung

sodium chloride

sulfolane

phosphoryl chloride

tert-butyl 4-oxo-3,4,5,6,7,9-hexahydro-8H-pyrimido[5′,4′:4,5]thieno[2,3-c]azepine-8-carboxylate

→

title compound

Ausbeute 80.0%

tert-Butyl 4-chloro-5,6,7,9-tetrahydro-8H-pyrimido[5′,4′:4,5]thieno[2,3-c]azepine-8-carboxylate

Ausbeute 80.0%

Lösungsmittel

triethylamine

toluene

Triethylamine

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturthe reaction mixture was heated for 2 h to 65° C
2. 2
   TemperaturThe mixture was then cooled to rt
3. 3
   Temperaturcooled to 0° C
4. 4
   workup.STIRRINGthe mixture was stirred for 20 min
5. 5
   SonstigeThe organic layer was separated
6. 6
   Waschenwashed with water
7. 7
   Trocknendried over sodium sulfate
8. 8
   Sonstigethe solvent was removed in vacuo
9. 9
   SonstigeThe residue was triturated with tert-butyl methyl ether
10. 10
    Filtrationthe precipitate was collected by suction filtration

Vorschrift

To sulfolane (20 mL) was added phosphoryl chloride (7.40 g, 48.3 mmol). Triethylamine (4.88 g, 48.3 mmol) was added dropwise, and the mixture was stirred for 30 min at rt. Subsequently, tert-butyl 4-oxo-3,4,5,6,7,9-hexahydro-8H-pyrimido[5′,4′:4,5]thieno[2,3-c]azepine-8-carboxylate from Example 78A (5.17 g, 16.1 mmol) was added, and the reaction mixture was heated for 2 h to 65° C. The mixture was then cooled to rt, and triethylamine (7.0 mL) was added. It was diluted with toluene and cooled to 0° C. Half-saturated aqueous sodium chloride solution was added, and the mixture was stirred for 20 min. The organic layer was separated, washed with water and dried over sodium sulfate, and the solvent was removed in vacuo. The residue was triturated with tert-butyl methyl ether, and the precipitate was collected by suction filtration to yield 4.40 g (80%) of the title compound.

Quelle