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

HRID 10675

Reaction equation

HRID 10675 reaction equation
[OH:1][C:2]1[C:9]([C:10]2[S:11][CH:12]=[CH:13][CH:14]=2)=[CH:8][C:5]([CH:6]=O)=[C:4]([O:15][CH3:16])[CH:3]=1.[C:17]([C:20]1[CH:28]=[CH:27][C:23]([C:24]([OH:26])=[O:25])=[CH:22][CH:21]=1)(=[O:19])[CH3:18].C[O-].[Li+].Cl>CN(C)C=O.CO.O.C(O)C>[OH:1][C:2]1[C:9]([C:10]2[S:11][CH:12]=[CH:13][CH:14]=2)=[CH:8][C:5](/[CH:6]=[CH:18]/[C:17]([C:20]2[CH:28]=[CH:27][C:23]([C:24]([OH:26])=[O:25])=[CH:22][CH:21]=2)=[O:19])=[C:4]([O:15][CH3:16])[CH:3]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 114704-Acetylbenzoic AcidHCID 4177230Lithium methanolateHCID 161159104-Hydroxy-2-methoxy-5-thiophen-2-yl-benzaldehyde

Product 1

HCID 101939834-[3E-(4-Hydroxy-2-methoxy-5-thiophen-2-yl-phenyl)-acryloyl]-benzoic acidYield 5%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 21901440N,N-dimethylformamide methanolSolvent

Procedure

4-Hydroxy-2-methoxy-5-thiophen-2-yl-benzaldehyde (Ex-47B, 0.30 g, 0.86 mmol) and 4-acetylbenzoic acid (0.13 g, 0.86 mmol) were dissolved in a dimethylformamide-methanol solution (6 mL, 7:3). After complete dissolution, lithium methoxide (0.12 g, 3.3 mmol) was added and the resulting red slurry was stirred in the dark at room temperature for 18 h. The mixture was diluted with water (15 mL), acidified with a 1 N hydrochloric acid solution, and extracted with ethyl acetate (4×25 mL). The combined organic extracts were dried over sodium sulfate and evaporated to dryness. The crude oil was subjected to silica gel chromatography (CH2Cl2:MeOH, 20:1) to yield an orange solid containing residual amounts of starting acid. The solid was taken up in ethyl alcohol (5 mL) to remove acid impurity and the resulting precipitate was collected on filter paper and dried in vacuo to yield 0.010 g (5%) of the title compound as an orange solid, mp 243° C. (dec). 1H-NMR (300 MHz, DMSO-d6) δ 8.18–8.23 (m, 3H), 8.06–8.09 (m, 2H), 8.02 (s, 1H), 7.85 (d, 1H, J=15.6 Hz), 7.68 (d, 1H, J=3.6 Hz), 7.47 (d, 1H, J=5.1 Hz), 7.11 (dd, 1H, J=5.1, 3.6 Hz), 6.67 (s, 1H), 4.13 (s, 1H), 3.89 (s, 3H). MS (ESI) m/z=381 ([M+H]30 , 100%). HRMS (ESI) Calcd. for C21H16O5S: 381.0796. Found: 381.0800.

Workup

  1. additionwas added
  2. extractionextracted with ethyl acetate (4×25 mL)
  3. dry with materialThe combined organic extracts were dried over sodium sulfate
  4. customevaporated to dryness
  5. customto yield an orange solid
  6. additioncontaining residual amounts
  7. customto remove acid impurity
  8. customthe resulting precipitate was collected
  9. filtrationon filter paper
  10. customdried in vacuo

Sources & evidence

ORD record
ord-a7aa117440654800b740f7e31e8883ad
Source dataset
uspto-grants-2006_08
Patent number
US07094801B2

Linked notes

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