Reaktion #158405

Reaktionsgleichung

1-(4-cyanobenzyl)azetidine-3-carboxylic acid

tert-butanol

EDC

→

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

Ausbeute 86.0%

Lösungsmittel

dichloroethane

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe volatiles were removed under reduced pressure
2. 2
   Sonstigethe residue was partitioned between ethyl acetate (250 mL)
3. 3
   WaschenThe organic layer was washed with water (250 mL)
4. 4
   Waschenwashed with brine (100 mL)
5. 5
   Trocknendried over anhydrous magnesium sulfate
6. 6
   EinengenConcentration under reduced pressure
7. 7
   Sonstigeafforded a light yellow oil which
8. 8
   Sonstigewas chromatographed on a 5×15 cm silica gel column
9. 9
   Wascheneluting with a 0-40% ethyl acetate/hexane gradient

Vorschrift

To a mixture of 1-(4-cyanobenzyl)azetidine-3-carboxylic acid (3.25 g, 15.0 mmol), DMAP (1.84 g, 15.0 mmol), and tert-butanol (14.1 mL, 150 mmol) in dichloroethane (150 mL) was added EDC (4.32 g, 22.5 mmol), and the reaction mixture was allowed to stir over the weekend. The volatiles were removed under reduced pressure, and the residue was partitioned between ethyl acetate (250 mL) and a saturated aqueous solution of sodium bicarbonate (250 mL). The organic layer was washed with water (250 mL), washed with brine (100 mL), and dried over anhydrous magnesium sulfate. Concentration under reduced pressure afforded a light yellow oil which was chromatographed on a 5×15 cm silica gel column, eluting with a 0-40% ethyl acetate/hexane gradient to give tert-butyl 1-(4-cyanobenzyl)azetidine-3-carboxylate (3.5 g, 12.9 mmol, 86% yield) as a colorless liquid. HPLC retention time=1.38 minutes (YMC-Combi 4.6×50 mm S-5 ODS column) eluting with 10-90% aqueous methanol+0.2% phosphoric acid over a 4 minute gradient. MS: (M+H)=273.18. 1H NMR (400 MHz, CDCl3) δ ppm 1.46 (s, 9H), 3.26 (m, 3H), 3.52 (m, 2H), 3.66 (s, 2H), 7.39 (d, J=8.3 Hz, 2H), and 7.60 (d, J=8.3 Hz, 2H).

Quelle