Reaktion #43398

Reaktionsgleichung

(4R/S)-3-fluoro-4-hydroxy-4-(hydroxymethyl)-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one

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

triethylamine

para-toluenesulphonyl chloride

dibutyltin oxide

→

[(4R/S)-3-Fluoro-4-hydroxy-7-oxo-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-4-yl]methyl 4-methylbenzenesulfonate

Lösungsmittel

dichloromethane tetrahydrofuran N,N-dimethylformamide

Water

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigethe organic phase was separated
2. 2
   Waschenwashed with saturated aqueous sodium bicarbonate
3. 3
   Sonstigeseparated
4. 4
   Trocknendried over magnesium sulphate
5. 5
   Sonstigeevaporated under vacuum
6. 6
   SonstigeThe residue was chromatographed on silica eluting with 0-100% ethyl acetate in dichloromethane

Vorschrift

A mixture of (4R/S)-3-fluoro-4-hydroxy-4-(hydroxymethyl)-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one (553 mg, 2.3 mmol) (racemic material, prepared from 3-fluoro-4-methylidene-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one using AD mix alpha/beta in a similar manner to Example 1(e) Method A) in dichloromethane/tetrahydrofuran/N,N-dimethylformamide (19 ml19 ml/2 ml) was treated with triethylamine (0.5 ml, 3.5 mmol), para-toluenesulphonyl chloride (446 mg, 2.3 mmol) and dibutyltin oxide (29 mg, 0.1 mmol) and stirred at room temperature overnight. Water was then added, the organic phase was separated and washed with saturated aqueous sodium bicarbonate, separated, dried over magnesium sulphate and evaporated under vacuum. The residue was chromatographed on silica eluting with 0-100% ethyl acetate in dichloromethane then 0-10% methanol in ethyl acetate affording a white solid (321 mg, 35%).

Quelle