Water → 3-(4-methyl-3-nitrophenyl)-1,2,4-oxadiazol-5(4H)-one

HRID 405823Notes

Reaction equation

HRID 405823 reaction equation
[OH:1][N:2]=[C:3]([NH2:14])[C:4]1[CH:9]=[CH:8][C:7]([CH3:10])=[C:6]([N+:11]([O-:13])=[O:12])[CH:5]=1.CCN(C(C)C)C(C)C.Cl[C:25](Cl)([O:27]C(=O)OC(Cl)(Cl)Cl)Cl.O>O1CCCC1>[CH3:10][C:7]1[CH:8]=[CH:9][C:4]([C:3]2[NH:14][C:25](=[O:27])[O:1][N:2]=2)=[CH:5][C:6]=1[N+:11]([O-:13])=[O:12]

Participants

6

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 94429TriphosgeneHCID 73711052N'-hydroxy-4-methyl-3-nitrobenzimidamide

Product 1

HCID 1363340393-(4-methyl-3-nitrophenyl)-1,2,4-oxadiazol-5(4H)-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of (Z)—N′-hydroxy-4-methyl-3-nitrobenzimidamide (27) (30 g, 153.71 mmol, 1.00 equiv) and DIEA (39.7 g, 307.18 mmol, 2.00 equiv) in tetrahydrofuran (300 mL) was added dropwise to a solution of triphosgene (18.2 g) in tetrahydrofuran (50 mL). The reaction was stirred for 1 hour at room temperature then heated to reflux for an additional hour. The resulting solution was poured into 500 mL of water and extracted with 3×300 mL of ethyl acetate. The combined organic layers were washed with brine (3×200 mL), dried over anhydrous sodium sulfate, concentrated under vacuum, and purified by flash chromatography (DCM/MeOH=20:1) to afford of 3-(4-methyl-3-nitrophenyl)-1,2,4-oxadiazol-5(4H)-one as a pale yellow solid (106). MS m/z 222.1 (M+1)+.

Workup

  1. temperaturethen heated
  2. temperatureto reflux for an additional hour
  3. extractionextracted with 3×300 mL of ethyl acetate
  4. washThe combined organic layers were washed with brine (3×200 mL)
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated under vacuum
  7. custompurified by flash chromatography (DCM/MeOH=20:1)

Sources & evidence

ORD record
ord-9d4bb5d8274f46bbbc253be5026e72ae
Source dataset
uspto-grants-2014_06
Patent number
US08754071B2

Reaction notes

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