Hydrochloric Acid → 5-[5-(2-Hydroxyphenyl)[1,2,4]oxadiazol-3-yl]pentanoic Acid

HRID 1039190Notes

Reaction equation

HRID 1039190 reaction equation
[OH-].[Na+].[OH:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[C:10]1[O:14][N:13]=[C:12]([CH2:15][CH2:16][CH2:17][CH2:18][C:19]([O:21]C)=[O:20])[N:11]=1.Cl>O.CO>[OH:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[C:10]1[O:14][N:13]=[C:12]([CH2:15][CH2:16][CH2:17][CH2:18][C:19]([OH:21])=[O:20])[N:11]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 136400600Methyl 5-[5-(2-hydroxyphenyl)[1,2,4]oxadiazol-3-yl]pentanoate

Product 1

HCID 1364006015-[5-(2-Hydroxyphenyl)[1,2,4]oxadiazol-3-yl]pentanoic AcidYield 97.4%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

Add boron tribromide (4.9 mL, 51.7 mmol) dropwise to a stirred solution of methyl 5-[5-(2-methoxyphenyl)[1,2,4]oxadiazol-3-yl]pentanoate (3.0 g, 10.3 mmol) in methylene chloride (70 mL) at 0° C. under nitrogen. Allow to warm to room temperature and stir for 5 hours. Cool the mixture to 0° C., 1 add methanol (20 mL) dropwise and allow to warm to room temperature. Remove the solvents under reduced pressure and purify the residue by flash column chromatography on silica gel, eluting with ethyl acetate/hexanes (1:9), to provide methyl 5-[5-(2-hydroxyphenyl)[1,2,4]oxadiazol-3-yl]pentanoate, which is used without further purification. Add a solution of sodium hydroxide (800 mg, 20 mmol) in water (15 mL) to a solution of methyl 5-[5-(2-hydroxyphenyl)[1,2,4]oxadiazol-3-yl]pentanoate (2.6 g, 9.4 mmol) in methanol (30 mL) at room temperature and stir the mixture for 2 hours. Adjust the pH of the mixture to 2 with 1 N HCl and extract with ethyl acetate (2×150 mL). Wash the combined organic extracts with water (3×150 mL), dry over sodium sulfate and remove the solvent under reduced pressure. Triturate the residue with hexanes/ethyl acetate and collect the solids by vacuum filtration to afford the title compound (2.4 g, 89% over two steps). APCI MS m/z 261 [C13H14N2O4−H]−.

Workup

  1. customis used without further purification
  2. extractionextract with ethyl acetate (2×150 mL)
  3. washWash the combined organic extracts with water (3×150 mL)
  4. dry with materialdry over sodium sulfate
  5. customremove the solvent under reduced pressure
  6. customTriturate the residue with hexanes/ethyl acetate
  7. customcollect the solids
  8. filtrationby vacuum filtration

Sources & evidence

ORD record
ord-22f5828d5ff6438fa4e55ef682762e56
Source dataset
uspto-grants-2013_10
Patent number
US08552039B2

Reaction notes

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