5-Bromo-2,4-dimethoxybenzaldehyde → 2,4-Dimethoxy-5-thien-2-ylbenzaldehyde

HRID 1270207Notes

Reaction equation

HRID 1270207 reaction equation
Br[C:2]1[C:3]([O:12][CH3:13])=[CH:4][C:5]([O:10][CH3:11])=[C:6]([CH:9]=1)[CH:7]=[O:8].[S:14]1[CH:18]=[CH:17][CH:16]=[C:15]1B(O)O>C1COCC1>[CH3:11][O:10][C:5]1[CH:4]=[C:3]([O:12][CH3:13])[C:2]([C:15]2[S:14][CH:18]=[CH:17][CH:16]=2)=[CH:9][C:6]=1[CH:7]=[O:8]

Participants

4

Reactant 2

HCID 6683465-Bromo-2,4-dimethoxybenzaldehydeHCID 27339602-Thiopheneboronic acid

Product 1

HCID 161161832,4-Dimethoxy-5-thien-2-ylbenzaldehydeYield 94%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

An alternative procedure: 5-bromo-2,4-dimethoxybenzaldehyde (20.3 g), thiophene-2-boronic acid (11.6 g) and THF (200 mL) were sequentially charged into a clean reaction vessel fitted with a reflux condenser, mechanical stirrer and nitrogen inlet adapter. Nitrogen was bubbled into the resulting solution for 20 min followed by the sequential addition of KF (10.1 g), and Pd(tBu3P)2 (0.424 g). The solution was immediately heated to 60° C. and aged for 1.5 h. The reaction was diluted with H2O (200 mL) and transferred to a separatory funnel containing EtOAc (200 mL) and H2O (200 mL). The layers were cut and the aqueous layer was extracted with EtOAc (100 mL). The combined organic cuts were filtered through a pre-washed pad of solka floe (5 g). The pad of solka floe and spent catalyst were washed with fresh EtOAc (200 mL) and this wash combined with the batch. The resultant filtrate was concentrated to dryness. The crude product was dissolved in THF (38 mL) and crystallized upon heptane (152 mL) addition. The product was filtered and then dried to a constant weight in the vacuum oven (38° C., 20 mHg) affording 19.32 g (94% yield) of desired 2,4-dimethoxy-5-thiophen-2-yl-benzaldehyde as a light off-white solid. 1H-NMR identical as above.

Workup

  1. customfitted with a reflux condenser, mechanical stirrer and nitrogen inlet adapter
  2. customNitrogen was bubbled into the resulting solution for 20 min
  3. additionfollowed by the sequential addition of KF (10.1 g), and Pd(tBu3P)2 (0.424 g)
  4. additionThe reaction was diluted with H2O (200 mL)
  5. customtransferred to a separatory funnel
  6. additioncontaining EtOAc (200 mL) and H2O (200 mL)
  7. extractionthe aqueous layer was extracted with EtOAc (100 mL)
  8. filtrationThe combined organic cuts were filtered through a pre-washed pad of solka floe (5 g)
  9. washwere washed with fresh EtOAc (200 mL)
  10. concentrationThe resultant filtrate was concentrated to dryness
  11. dissolutionThe crude product was dissolved in THF (38 mL)
  12. customcrystallized upon heptane (152 mL) addition
  13. filtrationThe product was filtered
  14. customdried to a constant weight in the vacuum oven (38° C., 20 mHg)

Sources & evidence

ORD record
ord-4be48967304a496a8db0f4d68ad65390
Source dataset
uspto-grants-2007_04
Patent number
US07202247B2

Reaction notes

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