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

HRID 1639502Notes

Reaction equation

HRID 1639502 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:12][C:11]([C:13]([N:15]3[CH2:18][CH:17]([OH:19])[CH2:16]3)=[O:14])=[N:10][N:9]=2)=[CH:4][CH:3]=1.ClC1C=CC(C2OC(C(OC)=O)=NN=2)=CC=1.C(N(CC)CC)C.[CH3:43][S:44](Cl)(=[O:46])=[O:45]>ClCCl>[CH3:43][S:44]([O:19][CH:17]1[CH2:16][N:15]([C:13]([C:11]2[O:12][C:8]([C:5]3[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=3)=[N:9][N:10]=2)=[O:14])[CH2:18]1)(=[O:46])=[O:45]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 59563510(5-(4-Chlorophenyl)-1,3,4-oxadiazol-2-yl)(3-hydroxyazetidin-1-yl)methanoneHCID 66611314Methyl 5-(4-chlorophenyl)-1,3,4-oxadiazole-2-carboxylate

Product 1

HCID 595635071-(5-(4-Chlorophenyl)-1,3,4-oxadiazole-2-carbonyl)azetidin-3-yl methanesulfonateYield 75%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

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]+.

Workup

  1. temperaturewas cooled in an ice-bath
  2. additionAfter the addition
  3. customthe cooling bath was removed
  4. customThe reaction mixture was transferred to a reparatory funnel
  5. washwas washed with water
  6. customThe organic solution was dried (phase separator)
  7. customevaporated
  8. additionDichloromethane (50 mL) and diethyl ether (200 mL) were added
  9. filtrationthe solid product was collected by filtration
  10. washThe solid was washed twice with diethyl ether
  11. customdried in vacuo
  12. customThe product was purified
  13. washfirst eluting with dichloromethane
  14. additionwith a mixture of dichloromethane and methanol containing 2M NH3 (20:1)

Sources & evidence

ORD record
ord-c111659b8b8c44d481becf119795741e
Source dataset
uspto-grants-2012_02
Patent number
US08110566B2

Reaction notes

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