Acetic Anhydride → N-Acetyl-4-[3E-(5-benzo[b]thiophen-2-yl-2,4-dimethoxy-phenyl)-acryloyl]-benzamide

HRID 10718Notes

Reaction equation

HRID 10718 reaction equation
[S:1]1[C:5]([C:6]2[C:7]([O:27][CH3:28])=[CH:8][C:9]([O:25][CH3:26])=[C:10](/[CH:12]=[CH:13]/[C:14]([C:16]3[CH:24]=[CH:23][C:19]([C:20]([NH2:22])=[O:21])=[CH:18][CH:17]=3)=[O:15])[CH:11]=2)=[CH:4][C:3]2[CH:29]=[CH:30][CH:31]=[CH:32][C:2]1=2.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[C:43](OC(=O)C)(=[O:45])[CH3:44]>C1COCC1>[C:43]([NH:22][C:20](=[O:21])[C:19]1[CH:23]=[CH:24][C:16]([C:14](=[O:15])/[CH:13]=[CH:12]/[C:10]2[CH:11]=[C:6]([C:5]3[S:1][C:2]4[CH:32]=[CH:31][CH:30]=[CH:29][C:3]=4[CH:4]=3)[C:7]([O:27][CH3:28])=[CH:8][C:9]=2[O:25][CH3:26])=[CH:17][CH:18]=1)(=[O:45])[CH3:44]

Participants

5

Reactant 3

HCID 7918Acetic AnhydrideHCID 2733832Lithium HexamethyldisilazideHCID 161157574-[3E-(5-Benzo[b]thiophen-2-yl-2,4dimethoxy-phenyl)-acryloyl]-benzamide

Product 1

HCID 16115758N-Acetyl-4-[3E-(5-benzo[b]thiophen-2-yl-2,4-dimethoxy-phenyl)-acryloyl]-benzamideYield 29.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

A suspension of 4-[3E-(5-benzo[b]thiophen-2-yl-2,4-dimethoxy-phenyl)-acryloyl]-benzamide (Ex-93, 0.5 g, 1.13 mmol) in THF (15 mL) was cooled to −78° C. followed by addition of lithium bis(trimethylsilyl)amide (1.0 M in THF, 2.3 mL, 2.3 mmol). The mixture was stirred at this temperature for 1 hour and warmed up to 0° C. Acetic anhydride (0.48 mL, 6.8 mmol) was then added dropwise. After the addition was complete the reaction mixture was warmed up to ambient temperature and stirred for 2 hours. The reaction was quenched with water. The aqueous solution was extracted with ethyl acetate. The combined extract was washed with NH4Cl, brine, dried and concentrated. The residue was purified by flash chromatography. Elution with 50% EtOAc/hexane gave the title compound as yellow solid (0.16 g, 29%), mp 228–229° C. 1H-NMR (CCDl3) δ 8.52 (s, 1H), 8.15–8.10 (m, 3H), 7.96 (d, J=7.6 Hz, 2H), 7.85–7.77 (m, 2H), 7.67 (s, 1H), 7.55 (d, J=16.7 Hz, 1H), 7.34–7.29 (m, 3H), 6.58 (s, 1H), 4.05 (s, 3H), 4.01 (s, 3H), 2.65 (s, 3H). MS m/z=485 (M+, 100%).

Workup

  1. temperaturewarmed up to 0° C
  2. additionAfter the addition
  3. temperaturewas warmed up to ambient temperature
  4. stirringstirred for 2 hours
  5. customThe reaction was quenched with water
  6. extractionThe aqueous solution was extracted with ethyl acetate
  7. extractionThe combined extract
  8. washwas washed with NH4Cl, brine
  9. customdried
  10. concentrationconcentrated
  11. customThe residue was purified by flash chromatography
  12. washElution with 50% EtOAc/hexane

Sources & evidence

ORD record
ord-17d25439f80f4b40abf3890546c5bd33
Source dataset
uspto-grants-2006_08
Patent number
US07094801B2

Reaction notes

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