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

HRID 1639501Notes

Reaction equation

HRID 1639501 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:12][C:11]([C:13]([O:15]CC)=O)=[N:10][N:9]=2)=[CH:4][CH:3]=1.[C-]#N.[Na+].Cl.[OH:22][CH:23]1[CH2:26][NH:25][CH2:24]1.C(N(CC)CC)C>CO.O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[O:12][C:11]([C:13]([N:25]3[CH2:26][CH:23]([OH:22])[CH2:24]3)=[O:15])=[N:10][N:9]=2)=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 8929Sodium CyanideHCID 27592903-Hydroxyazetidine hydrochlorideHCID 46742983Ethyl 5-(4-chlorophenyl)-1,3,4-oxadiazole-2-carboxylate

Product 1

HCID 59563510(5-(4-Chlorophenyl)-1,3,4-oxadiazol-2-yl)(3-hydroxyazetidin-1-yl)methanoneYield 90%

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 962WaterSolvent

Procedure

To a suspension of ethyl 5-(4-chlorophenyl)-1,3,4-oxadiazole-2-carboxylate—for preparation, see e.g. WO 97/05131—(0.53 g, 2.10 mmol) in dry methanol (10 mL) was added sodium cyanide (20 mg, 0.42 mmol). A solution of 3-hydroxyazetidine hydrochloride (0.38 g, 2.78 mmol) and triethylamine (0.39 mL, 2.78 mmol) in methanol (10 mL) was added at ambient temperature. The mixture was stirred for 2.5 h. Water (30 mL) was added and the mixture was extracted with dichloromethane. The organic layers were combined and evaporated to a white solid, which was treated with toluene (5 mL) and then filtered. The product was washed with toluene (5 mL) and then dried in vacuo. There was obtained 0.52 g (90%) of 2B as a solid. 1H NMR (400 MHz, CD3OD): δ 4.00 (dd, 1H), 4.46 (dd, 2H), 4.70 (m, 1H), 4.93 (dd, 1H), 7.62 (d, 2H), 8.11 (d, 2H), MS (APCI+) m/z 280 [M+H]+.

Workup

  1. customfor preparation
  2. extractionthe mixture was extracted with dichloromethane
  3. customevaporated to a white solid, which
  4. additionwas treated with toluene (5 mL)
  5. filtrationfiltered
  6. washThe product was washed with toluene (5 mL)
  7. customdried in vacuo

Sources & evidence

ORD record
ord-bb1d1108f0ec4bee80f3b58e069b1af9
Source dataset
uspto-grants-2012_02
Patent number
US08110566B2

Reaction notes

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