Reaktion #43403

Reaktionsgleichung

para-toluenesulphonic anhydride

1,1-dimethylethyl ((3R,45)-1-{(2R/S)-2-[3-chloro-6-(methyloxy)-1,5-naphthyridin-4-yl]-3-hydroxypropyl}-3-hydroxy-4-piperidinyl)carbamate

diisopropylethylamine

para-toluenesulphonic anhydride

→

3-Chloro-4-methylidene-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one

Lösungsmittel

dichloromethane

Reaktionsbedingungen

Aufarbeitung

1. 1
   WaschenAfter 2.5 days the mixture was washed with saturated aqueous sodium bicarbonate solution
2. 2
   ExtraktionThe aqueous phase was extracted with dichloromethane (2×)
3. 3
   Sonstigethe combined organic extracts dried
4. 4
   Sonstigeevaporated
5. 5
   SonstigeThe residue was chromatographed
6. 6
   Wascheneluting with methanol/dichloromethane
7. 7
   Sonstigeto give firstly the
8. 8
   Sonstigepartially purified title compound (0.84 g, 21%)
9. 9
   SonstigeThe partially purified title compound (0.84 g)
10. 10
    Sonstigewas further purified by chromatography
11. 11
    Wascheneluting with methanol/dichloromethane affording pure product (0.57 g)

Vorschrift

A solution of 1,1-dimethylethyl ((3R,45)-1-{(2R/S)-2-[3-chloro-6-(methyloxy)-1,5-naphthyridin-4-yl]-3-hydroxypropyl}-3-hydroxy-4-piperidinyl)carbamate (8.75 g, 18.7 mmol) and diisopropylethylamine (4.9 ml) in dichloromethane (90 ml) was treated at 0° C. under argon with para-toluenesulphonic anhydride (6.7 g, 20.6 mmol). After 3 hours at room temperature more para-toluenesulphonic anhydride (0.7 g) was added. After 2.5 days the mixture was washed with saturated aqueous sodium bicarbonate solution. The aqueous phase was extracted with dichloromethane (2×) and the combined organic extracts dried and evaporated. The residue was chromatographed, eluting with methanol/dichloromethane to give firstly the partially purified title compound (0.84 g, 21%) then 1,1-dimethylethyl {(3R,4S)-1-[(3-chloro-7-oxo-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-4-yl)methyl]-3-hydroxy-4-piperidinyl}carbamate (3.93 g, 48%). The partially purified title compound (0.84 g) was further purified by chromatography eluting with methanol/dichloromethane affording pure product (0.57 g).

Quelle