2-Methoxybenzoyl chloride → Methyl 5-[5-(2-methoxyphenyl)[1,2,4]oxadiazol-3-yl]pentanoate

HRID 1443685Notes

Reaction equation

HRID 1443685 reaction equation
[CH3:1][O:2][C:3]1[CH:11]=[CH:10][CH:9]=[CH:8][C:4]=1[C:5](Cl)=[O:6].O[NH:13][C:14]([CH2:16][CH2:17][CH2:18][CH2:19][C:20]([O:22][CH3:23])=[O:21])=[NH:15]>N1C=CC=CC=1>[CH3:1][O:2][C:3]1[CH:11]=[CH:10][CH:9]=[CH:8][C:4]=1[C:5]1[O:6][N:15]=[C:14]([CH2:16][CH2:17][CH2:18][CH2:19][C:20]([O:22][CH3:23])=[O:21])[N:13]=1

Participants

4

Reactant 2

HCID 889692-Methoxybenzoyl chlorideHCID 178500328methyl 5-(N-hydroxycarbamimidoyl)pentanoate

Product 1

HCID 59167762Methyl 5-[5-(2-methoxyphenyl)[1,2,4]oxadiazol-3-yl]pentanoateYield 34.4%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

Add 2-methoxybenzoyl chloride (5.20 g, 35 mmol) to a solution of methyl 5-(N-hydroxycarbamimidoyl)pentanoate (5.3 g, 34 mmol) in pyridine (50 mL) under nitrogen at 0° C. and then heat the mixture at reflux for 6 h. Remove the solvent under reduced pressure, dilute the residue with ethyl acetate and wash with 1 N HCl. Wash the combined organic extracts with brine, dry over sodium sulfate and remove the solvent under reduced pressure. Purify the residue by flash column chromatography on silica gel, eluting with ethyl acetate/hexanes (1:4), to afford methyl 5-[5-(2-methoxyphenyl)[1,2,4]oxadiazol-3-yl]pentanoate (3.4 g, 33% over two steps): 1H NMR (CDCl3) δ 1.7-1.85 (m, 2H), 1.85-2.00 (m, 2H), 2.35 (t, 2H), 2.95 (t, 2H), 3.65 (s, 3H), 3.95 (s, 3H), 7.00 (m, 2H), 7.45 (t, 1H), 8.00 (d, 1H).

Workup

  1. temperatureheat the mixture
  2. temperatureat reflux for 6 h
  3. customRemove the solvent under reduced pressure
  4. additiondilute the residue with ethyl acetate
  5. washwash with 1 N HCl
  6. washWash the combined organic extracts with brine
  7. dry with materialdry over sodium sulfate
  8. customremove the solvent under reduced pressure
  9. customPurify the residue by flash column chromatography on silica gel
  10. washeluting with ethyl acetate/hexanes (1:4)

Sources & evidence

ORD record
ord-61b7f2a084504359a1820526f64c7e68
Source dataset
uspto-grants-2010_02
Patent number
US07662771B2

Reaction notes

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