Reaktion #80554

Reaktionsgleichung

acetic acid

sodium cyanoborohydride

(R)-8-Fluoro-3-(N-isopropylamino)-5-methoxy-3,4-dihydro-2H-1-benzopyran

cyclobutanone

→

title compound

Ausbeute 77.0%

(R)-3-(N-Cyclobutyl-N-isopropylamino)-8-fluoro-5-methoxy-3,4-dihydro-2H-1-benzopyran

Ausbeute 77.0%

Lösungsmittel

methanol

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.ADDITIONadded
2. 2
   TemperaturThe reaction was cooled (ice-bath)
3. 3
   workup.ADDITIONwere added
4. 4
   workup.WAITAfter 24 h the pH-was again adjusted to 4-5
5. 5
   workup.STIRRINGto stir for 3 more days
6. 6
   FiltrationThe reaction was filtered
7. 7
   Sonstigesolvent was removed in vacuo
8. 8
   Extraktionextracted thrice with diethyl ether
9. 9
   TrocknenThe combined ether portions were dried (MgSO4)
10. 10
    Filtrationfiltered
11. 11
    Sonstigethe solvent removed in vacuo
12. 12
    Sonstigeto give the crude residue

Vorschrift

(R)-8-Fluoro-3-(N-isopropylamino)-5-methoxy-3,4-dihydro-2H-1-benzopyran (1.96 g, 8.19 mmol) was dissolved in anhydrous methanol (20 mL) and to this was cyclobutanone (6.1 mL, 81.9 mmol) added. The reaction was cooled (ice-bath) then sodium cyanoborohydride (2.0 g, 16.4 mmol) was added, the pH was adjusted to 4-5 with acetic acid, 3 Å molecular sieves were added and the reaction was allowed to stir at room temperature overnight. After 24 h the pH-was again adjusted to 4-5 and the reaction was allowed to stir for 3 more days. The reaction was filtered, solvent was removed in vacuo, the remains were taken into a 2M solution of NH3 and then extracted thrice with diethyl ether. The combined ether portions were dried (MgSO4) filtered, and the solvent removed in vacuo to give the crude residue. Chromatography on silica (eluent: 10% ethyl acetate/hexane) gave 1.60 g (77% yield) of the title compound as a clear oil. [α]21D =-95.1° (C=0.1; CHCl3). GC-MS (70 eV) M=293 (3%).

Quelle