Potassium Acetate → 6-(5-Benzylbenzofuran-2-yl)-2-methylnicotinaldehyde

HRID 2075271Notes

Reaction equation

HRID 2075271 reaction equation
[CH2:1]([C:8]1[CH:9]=[CH:10][C:11]2[O:15][C:14](B(O)O)=[CH:13][C:12]=2[CH:19]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([O-])(=O)C.[K+].Cl[C:26]1[CH:33]=[CH:32][C:29]([CH:30]=[O:31])=[C:28]([CH3:34])[N:27]=1>CCO>[CH2:1]([C:8]1[CH:9]=[CH:10][C:11]2[O:15][C:14]([C:26]3[CH:33]=[CH:32][C:29]([CH:30]=[O:31])=[C:28]([CH3:34])[N:27]=3)=[CH:13][C:12]=2[CH:19]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 517044Potassium AcetateHCID 447548676-Chloro-2-methylpyridine-3-carbaldehydeHCID 59595866HCID 59595866, compound

Product 1

HCID 584153726-(5-Benzylbenzofuran-2-yl)-2-methylnicotinaldehyde

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
80 °C

Procedure

In a sealed flask, a mixture of 5-benzylbenzofuran-2-ylboronic acid (525 mg, 2.1 mmol) and potassium acetate (0.41 g, 4.2 mmol) was set under argon, treated with bis{di(tbutyl)phenyl}palladium(II) dichloride (0.078 g, 0.12 mmol), followed by a solution of 6-chloro-2-methylnicotinaldehyde (0.29 g, 1.9 mmol) in EtOH (10 mL). The resulting suspension was degassed again and heated to 80° C. for 2 h. The mixture was cooled to 24° C., treated with EtOAc and washed with saturated aqueous NaHCO3 and brine (each 1×). The combined organic layers were dried over MgSO4 and evaporated. Purification by flash chromatography (hexanes to hexanes/EtOAc=9:1) gave 6-(5-Benzylbenzofuran-2-yl)-2-methylnicotinaldehyde as a pale yellow solid. 1H NMR (400 MHz, CDCl3) δ ppm 10.33 (s, 1H), 8.27 (d, J=8.0 Hz, 1H), 7.97-7.95 (m, 2H), 7.51-7.49 (m, 2H), 7.31-7.29 (m, 2H), 7.24-7.21 (m, 3H), 4.10 (s, 2H), 3.07 (s, 3H). MS (ESI) m/z: Calculated: 327.4; Observed: 328.1 (M++1).

Workup

  1. customThe resulting suspension was degassed again
  2. temperatureThe mixture was cooled to 24° C.
  3. additiontreated with EtOAc
  4. washwashed with saturated aqueous NaHCO3 and brine (each 1×)
  5. dry with materialThe combined organic layers were dried over MgSO4
  6. customevaporated
  7. customPurification by flash chromatography (hexanes to hexanes/EtOAc=9:1)

Sources & evidence

ORD record
ord-0cd37e6ea4f1470f9c562aedcf32acbd
Source dataset
uspto-grants-2011_04
Patent number
US07919519B2

Reaction notes

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