Dimethylformamide → 3-Chloro-4-(3-(3-chloro-4-isopropoxyphenyl)-1,2,4-oxadiazol-5-yl)benzonitrile

HRID 1172931Notes

Reaction equation

HRID 1172931 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]([C:11]#[N:12])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=O.CN(C=O)C.C(Cl)(=O)C(Cl)=O.[Cl:24][C:25]1[CH:26]=[C:27]([CH:32]=[CH:33][C:34]=1[O:35][CH:36]([CH3:38])[CH3:37])/[C:28](=[N:30]/O)/[NH2:29]>C(Cl)Cl>[Cl:1][C:2]1[CH:10]=[C:9]([CH:8]=[CH:7][C:3]=1[C:4]1[O:6][N:29]=[C:28]([C:27]2[CH:32]=[CH:33][C:34]([O:35][CH:36]([CH3:37])[CH3:38])=[C:25]([Cl:24])[CH:26]=2)[N:30]=1)[C:11]#[N:12]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 65578Oxalyl chloride2×HCID 2318942-Chloro-4-cyanobenzoic acidHCID 595565653-chloro-N'-hydroxy-4-propan-2-yloxybenzenecarboximidamide

Product 1

HCID 532462113-Chloro-4-(3-(3-chloro-4-isopropoxyphenyl)-1,2,4-oxadiazol-5-yl)benzonitrileYield 74.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a 250 mL RBF equipped with a stir bar was charged with 2-chloro-4-cyanobenzoic acid (3.0 g, 16.52 mmol), anhydrous DCM (80 mL), and DMF (0.064 mL, 0.826 mmol). Oxalyl chloride (8.26 mL, 16.52 mmol) (2M solution in DCM) was then added slowly and the mixture was stirred under nitrogen at ambient temperature. Upon addition of the oxalyl chloride, gas evolution began and the suspended solid began to dissolve. After about 2-3 hours, the reaction became translucent. The mixture was concentrated in vacuo. The resulting crude material was dissolved in pyridine (50 mL). To this was added (Z)-3-chloro-N′-hydroxy-4-isopropoxybenzimidamide (1.258 g, 5.50 mmol). The mixture was heated to about 100° C. under an atmosphere of nitrogen for about 16 hrs. The resulting mixture was cooled to ambient temperature. Pyridine was removed under reduced pressure and the resulting material was triturated in DCM and MeOH mixture (about 1:1). The resulting precipitate was left standing for a few minutes at ambient temperature then was collected via filtration, washed with a mixture of 1:1 DCM/MeOH, and then with straight MeOH and dried in a vacuum oven for about 48 hrs to yield 3-chloro-4-(3-(3-chloro-4-isopropoxyphenyl)-1,2,4-oxadiazol-5-yl)benzonitrile (1.529 g, 4.09 mmol) as a beige solid. 1H NMR (400 MHz, DMSO) δ ppm 8.39 (d, J=1.53 Hz, 1H), 8.35 (d, J=8.15 Hz, 1H), 8.09 (dd, J=8.14, 1.53 Hz, 1H), 8.05 (d, J=2.11 Hz, 1H), 8.00 (dd, J=8.63, 2.12 Hz, 1H), 7.39 (d, J=8.82 Hz, 1H), 4.82 (sept, J=6.04 Hz, 1H), 1.35 (d, J=6.01 Hz, 6H).

Workup

  1. customTo a 250 mL RBF equipped with a stir bar
  2. dissolutionto dissolve
  3. concentrationThe mixture was concentrated in vacuo
  4. dissolutionThe resulting crude material was dissolved in pyridine (50 mL)
  5. temperatureThe mixture was heated to about 100° C. under an atmosphere of nitrogen for about 16 hrs
  6. temperatureThe resulting mixture was cooled to ambient temperature
  7. customPyridine was removed under reduced pressure
  8. customthe resulting material was triturated in DCM
  9. waitThe resulting precipitate was left
  10. waitstanding for a few minutes at ambient temperature
  11. filtrationthen was collected via filtration
  12. washwashed with a mixture of 1:1 DCM/MeOH
  13. dry with materialwith straight MeOH and dried in a vacuum oven for about 48 hrs

Sources & evidence

ORD record
ord-fdf240a84091435cbf7808bf0610e533
Source dataset
uspto-grants-2010_11
Patent number
US07834039B2

Reaction notes

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