Reaktion #43592

Reaktionsgleichung

triethylamine

methanesulfonic anhydride

1,1-dimethylethyl (1-{2-[3-fluoro-6-(methyloxy)-1,5-naphthyridin-4-yl]-3-hydroxypropyl}-4-piperidinyl)carbamate

MeOH

→

1,1-Dimethylethyl {1-[(3-fluoro-7-oxo-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-4-yl)methyl]-4-piperidinyl}carbamate

Lösungsmittel

dichloromethane

dichloromethane

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturice-cooled
2. 2
   TemperaturAfter 1 hour the solution was heated
3. 3
   Temperaturto reflux for 2 days
4. 4
   Sonstigeevaporated
5. 5
   workup.DISSOLUTIONredissolved in chloroform (180 ml)
6. 6
   Temperaturcooled
7. 7
   Waschenwashed with aqueous sodium bicarbonate
8. 8
   Extraktionthe aqueous twice re-extracted with chloroform
9. 9
   SonstigeThe combined organic phases were dried
10. 10
    Sonstigeevaporated
11. 11
    SonstigeChromatography of the residue (methanol/dichloromethane gradient) and rechromatography of some impure fractions gave

Vorschrift

A solution of 1,1-dimethylethyl (1-{2-[3-fluoro-6-(methyloxy)-1,5-naphthyridin-4-yl]-3-hydroxypropyl}-4-piperidinyl)carbamate (18.28 g, containing some non-alcohol impurity and a little MeOH, judged to contain 40 mmol alcohol-containing compounds) in dichloromethane (180 ml) was stirred under argon, ice-cooled and treated with triethylamine (11.1 ml, 80 mmol) and methanesulfonic anhydride (8.7 g, 50 mmol). After 1 hour the solution was heated to reflux for 2 days, evaporated and redissolved in chloroform (180 ml). This solution was heated under argon at 55° C. for 3 days, cooled, washed with aqueous sodium bicarbonate and the aqueous twice re-extracted with chloroform. The combined organic phases were dried and evaporated. Chromatography of the residue (methanol/dichloromethane gradient) and rechromatography of some impure fractions gave the product (13.35 g, containing 12.5% dichloromethane by weight).

Quelle