Hydrochloric Acid → 4-Cyclobutyl-5-(5-ethoxy-4H-1,2,4-triazol-3-yl)-2-methylbenzonitrile

HRID 541360Notes

Reaction equation

HRID 541360 reaction equation
[NH2:1][C:2]1[O:6][C:5]([C:7]2[C:8]([CH:16]3[CH2:19][CH2:18][CH2:17]3)=[CH:9][C:10]([CH3:15])=[C:11]([CH:14]=2)[C:12]#[N:13])=[N:4][N:3]=1.[OH-].[K+].Cl.[CH3:23][CH2:24]O>>[CH:16]1([C:8]2[C:7]([C:5]3[NH:1][C:2]([O:6][CH2:23][CH3:24])=[N:3][N:4]=3)=[CH:14][C:11]([C:12]#[N:13])=[C:10]([CH3:15])[CH:9]=2)[CH2:19][CH2:18][CH2:17]1

Participants

5

Reactant 4

HCID 313Hydrochloric AcidHCID 702EthanolHCID 14797Potassium HydroxideHCID 682888425-(5-Amino-1,3,4-oxadiazol-2-yl)-4-cyclobutyl-2-methylbenzonitrile

Product 1

HCID 1784674894-Cyclobutyl-5-(5-ethoxy-4H-1,2,4-triazol-3-yl)-2-methylbenzonitrile

Conditions

Temperature
85 °C

Procedure

To a solution of 5-(5-amino-1,3,4-oxadiazol-2-yl)-4-cyclobutyl-2-methylbenzonitrile (219.6, 0.5 g, 2.0 mmol) in EtOH (40 ml) was added KOH (1.11 g, 20.0 mmol). The mixture was heated at 85° C. overnight. After cooling to ambient temperature, the mixture was neutralized to pH 7 with 1N HCl at 0° C. and then extracted with EtOAc (×2). The combined organic layers were dried (Na2SO4) and concentrated. The residue was purified using column (silica gel) chromatography (hexanes:EtOAc 1:1 to EtOAc). Yield: 0.2 g, white solid, 34%. m/z (ES+) 283 (M+H)+. 1H NMR (400 MHz, Chloroform-d) δ 7.84 (s, 1H), 7.35 (s, 1H), 4.48 (t, 2H), 4.19-4.10 (m, 1H), 2.58 (s, 3H), 2.30-2.19 (m, 2H), 2.11-1.95 (m, 3H), 1.85-1.76 (m, 1H), 1.45 (t, 3H).

Workup

  1. temperatureAfter cooling to ambient temperature
  2. extractionextracted with EtOAc (×2)
  3. dry with materialThe combined organic layers were dried (Na2SO4)
  4. concentrationconcentrated
  5. customThe residue was purified

Sources & evidence

ORD record
ord-1291fc772fb546609257d37116af8ba4
Source dataset
uspto-grants-2014_10
Patent number
US08871790B2

Reaction notes

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