Reaktion #489237

Reaktionsgleichung

(R)-2-azidomethyl-morpholine-4-carboxylic acid tert-butyl ester

HCl

6-butyl-5-(4-cyclohexyloxy-phenyl)-pyridazine-3-carboxylic acid pentafluorophenyl ester

→

((R)-2-azidomethyl-morpholin-4-yl)-[6-butyl-5-(4-cyclohexyloxy-phenyl)-pyridazin-3-yl]-methanone

Ausbeute 105.8%

Lösungsmittel

DCM

dioxane

ethyl acetate

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe volatiles were removed under reduced pressure
2. 2
   workup.DISSOLUTIONthe residue was dissolved in NMP (4 mL)
3. 3
   workup.STIRRINGthe reaction mixture was stirred at room temperature for 30 min
4. 4
   Waschenwashed with water
5. 5
   SonstigeThe organic layer was dried
6. 6
   Filtrationfiltered
7. 7
   Einengenconcentrated under reduced pressure
8. 8
   SonstigeThe residue was purified by flash silica gel column chromatography

Vorschrift

To a stirred solution of (R)-2-azidomethyl-morpholine-4-carboxylic acid tert-butyl ester (0.82 mmol, 0.2 g) in DCM (2 mL) was added 4 N HCl in dioxane (4 mL) and continued stirring at ambient temperature for 45 min. The volatiles were removed under reduced pressure, and the residue was dissolved in NMP (4 mL). To this was added 6-butyl-5-(4-cyclohexyloxy-phenyl)-pyridazine-3-carboxylic acid pentafluorophenyl ester (Example 93, 0.77 mmol, 0.4 g) followed by TEA (0.5 mL) and the reaction mixture was stirred at room temperature for 30 min. The reaction mixture was diluted with ethyl acetate (20 mL) and washed with water, followed by saturated sodium bicarbonate. The organic layer was dried, filtered, and concentrated under reduced pressure. The residue was purified by flash silica gel column chromatography using ethyl 30% acetate in hexanes to provide ((R)-2-azidomethyl-morpholin-4-yl)-[6-butyl-5-(4-cyclohexyloxy-phenyl)-pyridazin-3-yl]-methanone (0.39 g).

Quelle