Reaction #1726689

Reaction equation

3-hydroxyazetidine hydrochloride

triethylamine

ethyl 5-(4-methoxyphenyl)-1,3,4-oxadiazole-2-carboxylate

sodium cyanide

→

4A

Yield 77.0%

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

Yield 77.0%

Solvents

methanol

methanol

dichloromethane

Water

Conditions

Workup

1. 1
   OtherSome of the desired product precipitated
2. 2
   Filtrationwas filtered off
3. 3
   FiltrationThe two layers after filtration
4. 4
   Otherwere separated
5. 5
   Extractionthe aqueous phase was extracted twice with dichloromethane (30 mL)
6. 6
   DryingThe combined organic layers were dried over MgSO4
7. 7
   Otherthe solution was evaporated

Procedure

To a suspension of ethyl 5-(4-methoxyphenyl)-1,3,4-oxadiazole-2-carboxylate—see e.g. Journal fuer Praktische Chemie, 327, 109-116 (1985)—(0.50 g, 2.01 mmol) in dry methanol (10 mL) was added sodium cyanide (20 mg, 0.40 mmol). A solution of 3-hydroxyazetidine hydrochloride (0.26 g, 2.42 mmol) in methanol (2 mL) and then triethylamine (0.34 mL, 2.42 mmol) were added at ambient temperature. The reaction mixture was stirred at ambient temperature overnight. Water (20 mL) and dichloromethane (30 mL) were added. Some of the desired product precipitated and was filtered off. The two layers after filtration were separated and the aqueous phase was extracted twice with dichloromethane (30 mL). The combined organic layers were dried over MgSO4 and the solution was evaporated. In total, there was obtained 0.43 g (77%) of 4A as a solid. 1H NMR (400 MHz, DMSO-d6): δ 3.82 (dd, 1H), 3.84 (s, 3H), 4.30 (m, 2H), 4.55 (m, 1H), 4.77 (dd, 1H), 5.85 (d, 1H), 7.16 (d, 2H), 7.98 (d, 2H), MS (APCI+) m/z 276 [M+H]+.

Source