Oxalyl chloride → 5-[3-(5-Fluoro-2-methoxyphenyl)-1,2,4-oxadiazol-5-yl]-2-(2-methylpiperidin-1-yl)aniline

HRID 336308Notes

Reaction equation

HRID 336308 reaction equation
C(Cl)(=O)C(Cl)=O.[CH3:7][CH:8]1[CH2:13][CH2:12][CH2:11][CH2:10][N:9]1[C:14]1[CH:22]=[CH:21][C:17]([C:18]([OH:20])=O)=[CH:16][C:15]=1[N+:23]([O-])=O.[F:26][C:27]1[CH:28]=[CH:29][C:30]([O:37][CH3:38])=[C:31]([C:33](=[N:35]O)[NH2:34])[CH:32]=1.CCN(C(C)C)C(C)C>>[F:26][C:27]1[CH:28]=[CH:29][C:30]([O:37][CH3:38])=[C:31]([C:33]2[N:34]=[C:18]([C:17]3[CH:21]=[CH:22][C:14]([N:9]4[CH2:10][CH2:11][CH2:12][CH2:13][CH:8]4[CH3:7])=[C:15]([CH:16]=3)[NH2:23])[O:20][N:35]=2)[CH:32]=1

Participants

5

Reactant 4

HCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 431767024-(2-Methylpiperidin-1-yl)-3-nitrobenzoic acidHCID 723368235-fluoro-N'-hydroxy-2-methoxybenzenecarboximidamide

Product 1

HCID 252553775-[3-(5-Fluoro-2-methoxyphenyl)-1,2,4-oxadiazol-5-yl]-2-(2-methylpiperidin-1-yl)aniline

Procedure

Oxalyl chloride (190 mg; 1.5 mmol; 3 eq.), Intermediate 8 (132 mg; 0.5 mmol; 1 eq.), Intermediate 23 (92 mg; 0.5 mmol; 1 eq.) and DIEA (194 mg; 1.5 mmol; 3 eq.) were reacted according to general procedure 2. After purification by column chromatography c-hexane/ethyl acetate, 80/20), the residue was taken up in EtOH (20 mL) and stannous chloride dihydrate (564 mg; 2.5 mmol; 5 eq.) was added. The resulting mixture was stirred at reflux for 3 hours then concentrated in vacuo. The residue was partitioned between NaOH 0.05M and ethyl acetate. The phases were separated and the organic layer was washed with brine, dried over magnesium and concentrated in vacuo. Purification by column chromatography (c-hexane/ethyl acetate, 75/25) afforded the title compound as an off-white solid.

Workup

  1. customAfter purification by column chromatography c-hexane/ethyl acetate, 80/20), the residue
  2. temperatureat reflux for 3 hours
  3. concentrationthen concentrated in vacuo
  4. customThe residue was partitioned between NaOH 0.05M and ethyl acetate
  5. customThe phases were separated
  6. washthe organic layer was washed with brine
  7. dry with materialdried over magnesium
  8. concentrationconcentrated in vacuo
  9. customPurification by column chromatography (c-hexane/ethyl acetate, 75/25)

Sources & evidence

ORD record
ord-083da951ccf94ad2850100d24f1d92a3
Source dataset
uspto-grants-2014_11
Patent number
US08889668B2

Reaction notes

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