Reaction #312623

Reaction equation

2-(2,6-Dimethyl-morpholin-4-yl)-3,4-difluoro-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzaldehyde

sodium carbonate

acetonitrile water

iodopyrazine

→

off-white solid

Yield 39.5%

2-(2,6-Dimethyl-morpholin-4-yl)-3,4-difluoro-5-pyrazin-2-yl-benzaldehyde

Yield 39.5%

Solvents

EtOAc

water

Conditions

Workup

1. 1
   TemperatureThe mixture was cooled to room temperature
2. 2
   OtherThe phases were separated
3. 3
   Extractionthe aqueous phase was re-extracted with EtOAc (×2)
4. 4
   DryingThe combined organic layers were dried over MgSO4
5. 5
   Concentrationconcentrated
6. 6
   Otherto give a brown oil
7. 7
   OtherPurification on silica gel (hexane/EtOAc 9/1, 8/2

Procedure

To a suspension of 2-(2,6-Dimethyl-morpholin-4-yl)-3,4-difluoro-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzaldehyde (11.5 g, 29.1 mmol) and sodium carbonate (8.8 g, 83.1 mmol) in previously degassed acetonitrile/water (1/1) mixture (140 mL) was added iodopyrazine (5.7 g, 27.7 mmol) under nitrogen. Bis-(triphenylphosphine)-dichloro-palladium-(II) (758 mg, 1.08 mmol) was added at room temperature and the reaction was heated overnight at 85° C. The mixture was cooled to room temperature, diluted with EtOAc and water. The phases were separated and the aqueous phase was re-extracted with EtOAc (×2). The combined organic layers were dried over MgSO4 and concentrated to give a brown oil. Purification on silica gel (hexane/EtOAc 9/1, 8/2 then 7/3) yielded 3.65 g of an off-white solid. 1H-NMR (500 MHz, CDCl3) d 10.35 (s, 1H), 9.06 (t, 1H), 8.70 (dd, 1H), 8.57 (d, 1H) 8.32 (dd, 1H), 4.24 (m, 2H), 3.43 (dt, 2H), 3.05 (m, 2H), 1.32 (d, 6H).

Source