Sodium Hydroxide → 3-(1-Oxo-5-indanyl)-5-(4-(2-methylpropyl)phenyl)-1,2,4-oxadiazole

HRID 1352200Notes

Reaction equation

HRID 1352200 reaction equation
[CH3:1][CH:2]([CH3:13])[CH2:3][C:4]1[CH:12]=[CH:11][C:7]([C:8]([OH:10])=O)=[CH:6][CH:5]=1.Cl.CN(C)CCC[N:20]=[C:21]=[N:22]CC.O.ON1[C:32]2[CH:33]=[CH:34][CH:35]=[CH:36][C:31]=2N=N1.CC(OI1(OC(C)=O)(OC(C)=O)O[C:48](=[O:49])[C:47]2C=CC=C[C:42]1=2)=O.[OH-].[Na+]>CN(C=O)C.O.C(Cl)Cl>[O:49]=[C:48]1[C:32]2[C:31](=[CH:36][C:35]([C:21]3[N:20]=[C:8]([C:7]4[CH:6]=[CH:5][C:4]([CH2:3][CH:2]([CH3:1])[CH3:13])=[CH:12][CH:11]=4)[O:10][N:22]=3)=[CH:34][CH:33]=2)[CH2:42][CH2:47]1

Participants

9

Reactant 5

HCID 14798Sodium HydroxideHCID 381114-Isobutylbenzoic acidHCID 159087TriacetoxyperiodinaneHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrate

Product 1

HCID 211000243-(1-Oxo-5-indanyl)-5-(4-(2-methylpropyl)phenyl)-1,2,4-oxadiazoleYield 38%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of 4-(2-methylpropyl)benzoic acid (2.74 g, 15.44 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (2.95 g, 15.44 mmol) and 1-hydroxybenzotriazole hydrate (2.08 g, 15.44 mmol) in DMF (50 mL) was stirred at rt for 30 min. N-Hydroxy (1-hydroxy-5-indanyl)amidine (from Step B) was added and the reaction was first stirred at rt for 1 h, then heated to 80° C. for 18 h. The reaction was cooled, diluted with water (100 mL) and the product extracted into methylene chloride (2×100 mL). The combined organics were dried over magnesium sulfate and concentrated in vacuo to give an oil. This oil was dissolved in methylene chloride (30 mL) and Dess-martin periodinane (5 g) was added. After stirring for 1 h, 2N NaOH (100 mL) was added to the reaction and the product extracted into methylene chloride (3×100 mL). The combined organics were dried over magnesium sulfate and concentrated in vacuo. Silica gel chromatography eluting with 15% ethyl acetate/hexanes gave 1.6 g (4.48 mmol) of the title compound as a yellow solid: 1H NMR (500 MHz, CDCl3) δ 8.31 (s, 1H), 8.20 (d, J=8.0 Hz, 1H), 8.13 (d, J=8.2 Hz, 2H), 7.88 (d, J=8.0 Hz, 1H), 7.34 (d, J=8.3 Hz, 2H), 3.25 (t, J=6.0 Hz, 2H), 2.77 (t, J=6.0 Hz, 2H), 2.58 (d, J=7.1 Hz, 2H), 1.90–1.98 (m, 1H), 0.94 (d, J=6.6 Hz, 6H); ESI-MS 333.1 (M+H).

Workup

  1. temperatureheated to 80° C. for 18 h
  2. temperatureThe reaction was cooled
  3. extractionthe product extracted into methylene chloride (2×100 mL)
  4. dry with materialThe combined organics were dried over magnesium sulfate
  5. concentrationconcentrated in vacuo
  6. customto give an oil
  7. stirringAfter stirring for 1 h
  8. extractionthe product extracted into methylene chloride (3×100 mL)
  9. dry with materialThe combined organics were dried over magnesium sulfate
  10. concentrationconcentrated in vacuo
  11. washSilica gel chromatography eluting with 15% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-9a19436e924943c1a71926fd840d24f5
Source dataset
uspto-grants-2007_05
Patent number
US07220734B2

Reaction notes

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