3-Bromo-4,5-dimethoxybenzaldehyde → 3,4-Dimethoxy-5-thien-2-yl-benzaldehyde

HRID 10617

Reaction equation

HRID 10617 reaction equation
Br[C:2]1[C:3]([O:12][CH3:13])=[C:4]([O:10][CH3:11])[CH:5]=[C:6]([CH:9]=1)[CH:7]=[O:8].[S:14]1[CH:18]=[CH:17][CH:16]=[C:15]1B(O)O>COCCOC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(=O)([O-])[O-].[Na+].[Na+]>[CH3:11][O:10][C:4]1[CH:5]=[C:6]([CH:9]=[C:2]([C:15]2[S:14][CH:18]=[CH:17][CH:16]=2)[C:3]=1[O:12][CH3:13])[CH:7]=[O:8]

Participants

6

Reactant 2

HCID 813793-Bromo-4,5-dimethoxybenzaldehydeHCID 27339602-Thiopheneboronic acid

Product 1

HCID 219809853,4-Dimethoxy-5-thien-2-yl-benzaldehydeYield 91%

Reagents, catalysts & solvents 3

HCID 10340Sodium CarbonateCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

Ex-1D: A solution of 5-bromo-3,4-dimethoxybenzaldehyde (10.23 g, 41.7 mmol) in 359 mL of ethylene glycol dimethyl ether was purged with nitrogen gas for 30 min. The solution was treated with tetrakis(triphenylphosphine)palladium(0) (5.0 g, 4.3 mmol), thiophene-2-boronic acid (8.01 g, 62.6 mmol), and a solution of 2 N sodium carbonate 72 mL, 3.45 mmol). The reaction was refluxed for 16 h. The reaction mixture was concentrated, diluted with an aqueous solution of saturated sodium bicarbonate (75 mL), and extracted with dichloromethane (2×100 mL). The organic layer was dried over sodium sulfate and concentrated to a brown solid. The crude material was purified by silica gel chromatography (1:1 ethyl acetate/hexanes) to give 9.42 g (90%) of the desired 3,4-dimethoxy-5-(thien-2-yl)benzaldehyde product. 1H-NMR (300 MHz, CDCl3) δ 9.94 (s, 1H), 7.79 (d, 1H), 7.57 (dd, 1H), 7.41 (d, 1H), 7.36 (d, 1H), 7.13 (dd, 1H), 3.97 (s, 3H), 3.93 (s, 3H).

Workup

  1. temperatureThe reaction was refluxed for 16 h
  2. concentrationThe reaction mixture was concentrated
  3. additiondiluted with an aqueous solution of saturated sodium bicarbonate (75 mL)
  4. extractionextracted with dichloromethane (2×100 mL)
  5. dry with materialThe organic layer was dried over sodium sulfate
  6. concentrationconcentrated to a brown solid
  7. customThe crude material was purified by silica gel chromatography (1:1 ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-ffe68f0513c241bd8c2d2a4b859c46bf
Source dataset
uspto-grants-2006_08
Patent number
US07094801B2

Linked notes

Loading…