Reaction #312626

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

2-bromo-5-iodo-pyrazine

→

product

Yield 64.5%

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

Yield 64.5%

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
   OtherPurified by column chromatography
7. 7
   Washeluting with ethyl acetate in hexanes (5-40%)

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 (Example 22, step 2) (1.5 g, 3.9 mmol) and sodium carbonate (1.1 g, 11 mmol) in previously degassed acetonitrile/water (1/1) mixture (4 mL) was added 2-bromo-5-iodo-pyrazine (1.0 g, 3.5 mmol) under nitrogen. Bis-(triphenylphosphine)-dichloro-palladium-(II) (0.099 g, 0.14 mmol) was added at room temperature and the reaction was heated overnight at 55° C. The mixture was cooled to room temperature, diluted with EtOAc and water then neutralized. The phases were separated and the aqueous phase was re-extracted with EtOAc (×2). The combined organic layers were dried over MgSO4 and concentrated. Purified by column chromatography eluting with ethyl acetate in hexanes (5-40%) to obtain 931 mgs of product. 1H NMR (400 MHz, CHLOROFORM-d) d ppm 1.28 (d, J=6.4 Hz, 6H), 3.02 (m, 2H), 3.40 (m, 2H), 4.19 (m, 2H), 8.28 (dd, J=8.2, 2.1 Hz, 1H), 8.74 (d, J=1.4 Hz, 1H), 8.78 (m, 1H), 10.29 (s, 1H) ; MS(APCl+) m/z 412, 414 (MH+).

Source