Hydrochloric Acid → 3-Methyl-5-(4-nitrophenoxymethyl)-1,2,4-oxadiazole

HRID 1770815Notes

Reaction equation

HRID 1770815 reaction equation
[N+:1]([C:4]1[CH:14]=[CH:13][C:7]([O:8][CH2:9][C:10]([OH:12])=O)=[CH:6][CH:5]=1)([O-:3])=[O:2].Cl.C(N(CC)CC)C.[C:23](=[N:26]O)([NH2:25])[CH3:24].CCN=C=NCCCN(C)C.Cl.Cl.C(N(C(C)C)CC)(C)C>O1CCCC1>[CH3:24][C:23]1[N:26]=[C:10]([CH2:9][O:8][C:7]2[CH:6]=[CH:5][C:4]([N+:1]([O-:3])=[O:2])=[CH:14][CH:13]=2)[O:12][N:25]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 15720(4-Nitrophenoxy)acetic acidHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 86609722HCID 86609722, compound

Product 1

HCID 220604453-Methyl-5-(4-nitrophenoxymethyl)-1,2,4-oxadiazoleYield 60.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 4-nitrophenoxyacetic acid (12) (2.25 g, 11.4 mmol), acetamide oxime triethylamine hydrochloride salt (11, 5.85 g, 27.62 mmol), EDCl.HCl (4.37 g, 22.79 mmol) and diisopropylethylamine (7.42 g, 10 mL, 57.40 mmol) in anhydrous tetrahydrofuran (THF) (250 mL) was refluxed for 18 hours. The heterogeneous brown reaction mixture was then quenched with water and extracted with EtOAc (3×300 mL). The combined organic layers were washed successively with aqueous sodium bicarbonate (NaHCO3) and brine. The resulting organic phase was dried over anhydrous Na2SO4 and solvent was removed by using rotary evaporator. The resulting residue was purified by silica gel column chromatography to yield 1.62 g (60%) of the desired product, 3-methyl-5-(4-nitrophenoxymethyl)-1,2,4-oxadiazole (13a) as a white solid. 1H NMR (CDCl3, 300 MHz): δ 8.24 (d, 2H, J=8.8 Hz), 7.08 (d, 2H, J=8.8 Hz), 5.36 (s, 2H), 2.44 (s, 3H); LCMS (m/z): 236 (MH+).

Workup

  1. customThe heterogeneous brown reaction mixture was then quenched with water
  2. extractionextracted with EtOAc (3×300 mL)
  3. washThe combined organic layers were washed successively with aqueous sodium bicarbonate (NaHCO3) and brine
  4. dry with materialThe resulting organic phase was dried over anhydrous Na2SO4 and solvent
  5. customwas removed
  6. customevaporator
  7. customThe resulting residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-c7bf8eed8bf24fa7bd53592e6df43a97
Source dataset
uspto-grants-2016_02
Patent number
US09248190B2

Reaction notes

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