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

HRID 1616573Notes

Reaction equation

HRID 1616573 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-f15b06eca61a4ee1a9b435e32ad58c48
Source dataset
uspto-grants-2014_07
Patent number
US08765796B2

Reaction notes

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