Reaction #1726684

Reaction equation

methanesulfonyl chloride

2B

(5-(4-Chlorophenyl)-1,3,4-oxadiazol-2-yl)(3-hydroxyazetidin-1-yl)methanone

methyl 5-(4-chlorophenyl)-1,3,4-oxadiazole-2-carboxylate

Triethylamine

→

2C

Yield 75.0%

1-(5-(4-Chlorophenyl)-1,3,4-oxadiazole-2-carbonyl)azetidin-3-yl methanesulfonate

Yield 75.0%

Solvents

dichloromethane

Conditions

Workup

1. 1
   Temperaturewas cooled in an ice-bath
2. 2
   workup.ADDITIONAfter the addition
3. 3
   Otherthe cooling bath was removed
4. 4
   OtherThe reaction mixture was transferred to a reparatory funnel
5. 5
   Washwas washed with water
6. 6
   OtherThe organic solution was dried (phase separator)
7. 7
   Otherevaporated
8. 8
   workup.ADDITIONDichloromethane (50 mL) and diethyl ether (200 mL) were added
9. 9
   Filtrationthe solid product was collected by filtration
10. 10
    WashThe solid was washed twice with diethyl ether
11. 11
    Otherdried in vacuo
12. 12
    OtherThe product was purified
13. 13
    Washfirst eluting with dichloromethane
14. 14
    workup.ADDITIONwith a mixture of dichloromethane and methanol containing 2M NH3 (20:1)

Procedure

A suspension of 2B —which contained approximately 50% of methyl 5-(4-chlorophenyl)-1,3,4-oxadiazole-2-carboxylate as an impurity—(1.38 g, 2.47 mmol) in dichloromethane (50 mL) was cooled in an ice-bath. Triethylamine (0.51 mL, 3.70 mmol) was added followed by methanesulfonyl chloride (0.27 mL, 3.45 mmol). After the addition, the cooling bath was removed. The mixture was stirred for 7 h. The reaction mixture was transferred to a reparatory funnel and was washed with water followed by aqueous NaHCO3. The organic solution was dried (phase separator) and evaporated. Dichloromethane (50 mL) and diethyl ether (200 mL) were added and the solid product was collected by filtration. The solid was washed twice with diethyl ether and then dried in vacuo. The product was purified using flash column chromatography first eluting with dichloromethane and then with a mixture of dichloromethane and methanol containing 2M NH3 (20:1). There was obtained 0.66 g (75%) of 2C as a solid. 1H NMR (500 MHz, CDCl3): δ 3.13 (s, 3H), 4.43 (dd, 1H), 4.65 (dd, 1H), 4.87 (dd, 1H), 5.12 (dd, 1H), 5.41 (m, 1H), 7.53 (d, 2H), 8.10 (d, 2H), MS (APCI+) m/z 358 [M+H]+.

Source