Acetohydrazide → (E)-2-(4-((2-(4-fluoro-2-methylphenyl)-6-methoxybenzo[b]thiophen-3-yl)oxy)styryl)-5-methyl-1,3,4-oxadiazole

HRID 332861Notes

Reaction equation

HRID 332861 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:12][C:11]3[CH:13]=[C:14]([O:17][CH3:18])[CH:15]=[CH:16][C:10]=3[C:9]=2[O:19][C:20]2[CH:25]=[CH:24][C:23](/[CH:26]=[CH:27]/[C:28]([OH:30])=O)=[CH:22][CH:21]=2)=[C:4]([CH3:31])[CH:3]=1.[C:32]([NH:35][NH2:36])(=O)[CH3:33].O=P(Cl)(Cl)Cl>>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:12][C:11]3[CH:13]=[C:14]([O:17][CH3:18])[CH:15]=[CH:16][C:10]=3[C:9]=2[O:19][C:20]2[CH:21]=[CH:22][C:23](/[CH:26]=[CH:27]/[C:28]3[O:30][C:32]([CH3:33])=[N:35][N:36]=3)=[CH:24][CH:25]=2)=[C:4]([CH3:31])[CH:3]=1

Participants

4

Reactant 3

HCID 14039AcetohydrazideHCID 24813Phosphorus oxychlorideHCID 86730646(E)-3-(4-((2-(4-fluoro-2-methylphenyl)-6-methoxybenzo[b]thiophen-3-yl)oxy)phenyl)acrylic acid

Product 1

HCID 86730645(E)-2-(4-((2-(4-fluoro-2-methylphenyl)-6-methoxybenzo[b]thiophen-3-yl)oxy)styryl)-5-methyl-1,3,4-oxadiazoleYield 76.5%

Conditions

Temperature
100 °C

Procedure

To a 30 mL vial, (E)-3-(4-((2-(4-fluoro-2-methylphenyl)-6-methoxybenzo[b]thiophen-3-yl)oxy)phenyl)acrylic acid (100 mg, 0.230 mmol) and acetohydrazide (85 mg, 1.151 mmol) were dissolved in POCl3 (2 mL, 21.46 mmol) and the mixture was heated to 100° C. for 18 h. The reaction mixture was cooled to room temperature poured into ice. The solution was quenched with sat. sodium bicarb and diluted with DCM. The organic layer was collected (phase separator) and concentrated to provide the crude material. The crude product was purified by reverse phase HPLC (acidic condition, 0.1% TFA in 30-100% CH3CN/H2O) to afford (E)-2-(4-((2-(4-fluoro-2-methylphenyl)-6-methoxybenzo[b]thiophen-3-yl)oxy)styryl)-5-methyl-1,3,4-oxadiazole (83 mg, 0.176 mmol, 76% yield) as a white solid. 1H NMR (400 MHz, CD3OD) δ ppm=2.38 (s, 3H), 2.57 (s, 3H), 3.90 (s, 3H), 6.81-6.98 (m, 4H), 6.98-7.08 (m, 2H), 7.28-7.42 (m, 2H), 7.44-7.58 (m, 4H). LC/MS (m/z, MH+): 473.4.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. additionpoured into ice
  3. customThe solution was quenched with sat. sodium bicarb
  4. additiondiluted with DCM
  5. customThe organic layer was collected (phase separator)
  6. concentrationconcentrated
  7. customto provide the crude material
  8. customThe crude product was purified by reverse phase HPLC (acidic condition, 0.1% TFA in 30-100% CH3CN/H2O)

Sources & evidence

ORD record
ord-f4515d9c164e45269a29ba19ccd74d4a
Source dataset
uspto-grants-2014_11
Patent number
US08877801B2

Reaction notes

Loading…