Reaktion #2039105

Reaktionsgleichung

sodium cyanoborohydride

cyanide

tert-butyl azetidine-3-carboxylate acetic acid salt

4-formylbenzonitrile

→

tert-butyl 1-(4-cyanobenzyl)azetidine-3-carboxylate

Ausbeute 89.0%

Lösungsmittel

methanol

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturto warm to room temperature
2. 2
   EinengenThe reaction mixture was concentrated under reduced pressure
3. 3
   workup.ADDITIONthe residue was diluted with a 10% aqueous solution of sodium bicarbonate
4. 4
   Extraktionextracted with ethyl acetate
5. 5
   SonstigeThe organic layer was collected
6. 6
   Waschenwashed with brine
7. 7
   Trocknendried over anhydrous sodium sulfate
8. 8
   EinengenConcentration under reduced pressure
9. 9
   Sonstigefollowed by purification by silica gel chromatography

Vorschrift

To a solution of tert-butyl azetidine-3-carboxylate acetic acid salt (92.0 g, 0.423 mol) in methanol (1.0 L) at room temperature was added 4-formylbenzonitrile (50.8 g, 0.381 mol). The reaction mixture was cooled to 0° C., and sodium cyanoborohydride (28.8 g, 0.458 mol) was added portion-wise (caution: potential cyanide generation). The reaction mixture was allowed to warm to room temperature and was stirred overnight. The reaction mixture was concentrated under reduced pressure, and the residue was diluted with a 10% aqueous solution of sodium bicarbonate and extracted with ethyl acetate. The organic layer was collected, washed with brine, and dried over anhydrous sodium sulfate. Concentration under reduced pressure followed by purification by silica gel chromatography using a 20% mixture of ethyl acetate in petroleum ether afforded tert-butyl 1-(4-cyanobenzyl)azetidine-3-carboxylate (89%) (After chromatography, Int. 1-D contained a small amount of 4-hydroxymethylbenzonitrile but was taken forward to the next step without further purification). LC/MS M+1=273.18. 1H NMR (400 MHz, CDCl3) δ ppm 1.46 (s, 9H), 3.22-3.31 (m, 3H), 3.48-3.56 (m, 2H), 3.66 (s, 2H), 7.39 (d, J=8.28 Hz, 2H), and 7.60 (d, J=8.28 Hz, 2H).

Quelle