Reaktion #170221

Reaktionsgleichung

3-(4,4,4-Trifluorobutoxy)-azetidine

EDCI

HOBt

diisopropylethylamine

(E)-3-(7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)-acrylic acid hydrochloride

→

title product

(E)-6-(3-Oxo-3-(3-(4,4,4-trifluorobutoxy)azetidin-1-yl)prop-1-enyl)-3,4-dihydro-1,8-naphthyridin-2(1H)-one

Lösungsmittel

ethyl acetate

water

dimethylformamide

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe aqueous layer was separated
2. 2
   Extraktionextracted with ethyl acetate (2×50 mL)
3. 3
   WaschenThe combined organic phases were washed with a saturated solution of sodium chloride (3×100 mL)
4. 4
   Trocknendried over sodium sulfate
5. 5
   Einengenconcentrated to dryness
6. 6
   SonstigeThe residue was purified by chromatography on silica gel
7. 7
   SonstigeThe residue was finally triturated in diethylether

Vorschrift

3-(4,4,4-Trifluorobutoxy)-azetidine (129 mg, 0.59 mmol), EDCI (113 mg, 0.59 mmol), HOBt (80 mg, 0.59 mmol) and diisopropylethylamine (170 μL, 0.97 mmol) were successively added to a solution of (E)-3-(7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)-acrylic acid hydrochloride (100 mg, 0.039 mmol) in dimethylformamide (10 mL) at room temperature. The reaction mixture was stirred overnight then diluted with ethyl acetate (50 mL) and water (50 mL). The aqueous layer was separated and extracted with ethyl acetate (2×50 mL). The combined organic phases were washed with a saturated solution of sodium chloride (3×100 mL), dried over sodium sulfate and concentrated to dryness. The residue was purified by chromatography on silica gel using dichloromethane/methanol (95:5 to 9:1) as eluent. The residue was finally triturated in diethylether to give the title product as a pale yellow solid (52.5 mg, 35%).

Quelle