Reaction #1726680

Reaction equation

3-hydroxyazetidine hydrochloride

triethylamine

ethyl 5-phenyl-1,3,4-oxadiazole-2-carboxylate

sodium cyanide

→

1B

Yield 90.0%

(3-Hydroxyazetidin-1-yl)(5-phenyl-1,3,4-oxadiazol-2-yl)methanone

Yield 90.0%

Solvents

dichloromethane

water

methanol

methanol

Conditions

Workup

1. 1
   workup.ADDITIONwere added
2. 2
   OtherThe layers were separated
3. 3
   Extractionthe aqueous phase was extracted twice with dichloromethane (30 mL)
4. 4
   OtherThe combined organic layers were evaporated
5. 5
   workup.ADDITIONThe crude product was then treated with toluene (5 mL)
6. 6
   Filtrationfiltered
7. 7
   Washwashed with toluene (5 mL)
8. 8
   Otherdried in vacuo

Procedure

To a clear solution of ethyl 5-phenyl-1,3,4-oxadiazole-2-carboxylate (0.40 g, 1.83 mmol) in dry methanol (5 mL) was added sodium cyanide (18 mg, 0.37 mmol). A solution of 3-hydroxyazetidine hydrochloride (0.45 g, 2.84 mmol) and triethylamine (0.40 mL, 2.84 mmol) in methanol (5 mL) was added at ambient temperature. After stirring for 20 min water (20 mL) and dichloromethane (30 mL) were added. The layers were separated and the aqueous phase was extracted twice with dichloromethane (30 mL). The combined organic layers were evaporated. The crude product was then treated with toluene (5 mL), filtered, washed with toluene (5 mL) and dried in vacuo. There was obtained 0.40 g (90%) of 1B as a solid. 1H NMR (400 MHz, DMSO-d6): δ 3.84 (dd, 1H), 4.31 (m, 2H), 4.56 (m, 1H), 4.79 (dd, 1H), 5.87 (d, 1H), 7.64 (m, 3H), 8.05 (d, 2H), MS (APCI+) m/z 246 [M+H]−.

Source