Hydrochloric Acid → 4-[3E-(2,4-Dimethoxy-5-thiophen-2-yl-phenyl)-acryloyl]-benzoic acid

HRID 10624

Reaction equation

HRID 10624 reaction equation
[CH3:1][O:2][C:3]1[CH:10]=[C:9]([O:11][CH3:12])[C:8]([C:13]2[S:14][CH:15]=[CH:16][CH:17]=2)=[CH:7][C:4]=1[CH:5]=O.[C:18]([C:21]1[CH:29]=[CH:28][C:24]([C:25]([OH:27])=[O:26])=[CH:23][CH:22]=1)(=[O:20])[CH3:19].O(C)[Li].C(OC(C)=O)(C)C.Cl>O.CN(C=O)C.CO>[CH3:1][O:2][C:3]1[CH:10]=[C:9]([O:11][CH3:12])[C:8]([C:13]2[S:14][CH:15]=[CH:16][CH:17]=2)=[CH:7][C:4]=1/[CH:5]=[CH:19]/[C:18]([C:21]1[CH:29]=[CH:28][C:24]([C:25]([OH:27])=[O:26])=[CH:23][CH:22]=1)=[O:20]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 7915Isopropyl AcetateHCID 114704-Acetylbenzoic AcidHCID 161161832,4-Dimethoxy-5-thien-2-ylbenzaldehydeHCID 178419045HCID 178419045, compound

Product 1

HCID 103095954-[3E-(2,4-Dimethoxy-5-thiophen-2-yl-phenyl)-acryloyl]-benzoic acidYield 75%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

2,4-Dimethoxy-5-thiophen-2-yl-benzaldehyde from Ex-6A (7.81 g), 4-acetylbenzoic acid (4.9 g), MeOH (60 mL) and DMF (150 mL) were sequentially charged into a clean reaction vessel fitted with a stir bar and nitrogen inlet adapter. After complete dissolution LiOMe (4.60 g) was added and the resulting solution was aged for 5 h. The reaction was diluted with H2O (200 mL) and transferred to a separatory funnel containing iPrOAc (100 mL). The layers were cut and the aqueous layer was acidified to a pH of 1 with 3 N HCl. The resulting precipitate was filtered and then dried on the filter funnel under a stream of N2. The crude product was then dissolved in THF (60 mL) and crystallized with the addition of heptane (60 mL). The product was filtered and then dried to a constant weight in the vacuum oven affording 8.9 g (75% yield) of the title compound as a yellow solid, m.p. 213–216° C. 1H-NMR (300 MHz, CDCl3): 8.20 (d, 2H, J=8.5 Hz), 8.09 (d, 1H, J=16.1 Hz), 8.06 (d, 2H, J=8.5 Hz), 7.85 (s, 1H), 7.52 (d, 1H, J=16.1 Hz), 7.40 (m, 1H), 7.30 (dd, 1H, J=5.2 and 1.7 Hz), 7.08 (dd, 1H, J=5.2 and 3.6 Hz), 6.53 (s, 1H), 3.98 (s, 3H), 3.97 (s, 3H); EIMS m/z=394 (M+). Anal. calc. for C22H18O5S: C, 66.99; H, 4.60; S, 8.13; found: C, 66.71; H, 4.59; S, 8.10.

Workup

  1. customfitted with a stir bar and nitrogen inlet adapter
  2. additionwas added
  3. customtransferred to a separatory funnel
  4. filtrationThe resulting precipitate was filtered
  5. dry with materialdried on the filter funnel under a stream of N2
  6. dissolutionThe crude product was then dissolved in THF (60 mL)
  7. customcrystallized with the addition of heptane (60 mL)
  8. filtrationThe product was filtered
  9. customdried to a constant weight in the vacuum oven

Sources & evidence

ORD record
ord-2cfd49376d34445eab0e8f2771463ec3
Source dataset
uspto-grants-2006_08
Patent number
US07094801B2

Linked notes

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