4-Acetylbenzoic Acid → 4-[3E-{4-Fluoro-3-(thiophen-2-yl)-phenyl}-acryloyl]-benzoic acid

HRID 10630Notes

Reaction equation

HRID 10630 reaction equation
[F:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=O)=[CH:4][C:3]=1[C:10]1[S:11][CH:12]=[CH:13][CH:14]=1.[C:15]([C:18]1[CH:26]=[CH:25][C:21]([C:22]([OH:24])=[O:23])=[CH:20][CH:19]=1)(=[O:17])[CH3:16].[OH-].[Na+]>CN(C)C=O.O>[F:1][C:2]1[CH:9]=[CH:8][C:5](/[CH:6]=[CH:16]/[C:15]([C:18]2[CH:26]=[CH:25][C:21]([C:22]([OH:24])=[O:23])=[CH:20][CH:19]=2)=[O:17])=[CH:4][C:3]=1[C:10]1[S:11][CH:12]=[CH:13][CH:14]=1

Participants

6

Reactant 3

HCID 114704-Acetylbenzoic AcidHCID 14798Sodium HydroxideHCID 167688744-Fluoro-3-(thiophen-2-yl)benzaldehyde

Product 1

HCID 210416224-[3E-{4-Fluoro-3-(thiophen-2-yl)-phenyl}-acryloyl]-benzoic acidYield 53%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

4-Fluoro-3-thiophen-2-yl-benzaldehyde (1.0 g, 4.85 mmol, from Ex-20A) and 4-acetylbenzoic acid (0.80 g, 4.87 mmol) were dissolved in dimethylformamide (55 mL). Sodium hydroxide solution (5 N, 3.88 mL) was added in one portion, and the mixture was stirred at room temperature for 3 h. The reaction was diluted with water (100 mL) and washed with ethyl acetate (100 mL). The aqueous phase was acidified with conc. HCl and extracted with ethyl acetate (2×100 mL). The organic phase was dried over magnesium sulfate and concentrated under reduced pressure. Recrystallization from ethanol provided 0.90 g (53%) of the title compound as a solid, m.p. 242–244° C. 1H-NMR (300 MHz, d6-DMSO) δ 13.31 (bs, 1H), 8.32 (dd, 1H, J=8.2 and 2.0 Hz), 8.24 (d, 2H, J=8.2 Hz), 8.07 (d, 2H, J=7.9 Hz), 7.98 (d, 1H, J=16.1 Hz), 7.92 (m, 1H), 7.80 (d, 1H, J=16.1 Hz), 7.69–7.73 (m, 2H), 7.41 (dd, 1H, 10.8 and 9.2 Hz), 7.20 (m, 1H). MS m/z=352 ([M]+, 50%), 343 (100%). HRMS (EI) Calcd. for C20H13FO3S: 352.0569. Found: 352.0571.

Workup

  1. washwashed with ethyl acetate (100 mL)
  2. extractionextracted with ethyl acetate (2×100 mL)
  3. dry with materialThe organic phase was dried over magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customRecrystallization from ethanol

Sources & evidence

ORD record
ord-2a580c9cc4a04d5ca1251353720da926
Source dataset
uspto-grants-2006_08
Patent number
US07094801B2

Reaction notes

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