Reaction #312622

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

2-iodopyrazine

sodium carbonate

→

desired product

Yield 68.0%

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

Yield 68.0%

Solvents

CH3CN H2O

Conditions

Workup

1. 1
   OtherThe reaction mixture was then purged with nitrogen
2. 2
   OtherUpon completion the reaction was partitioned between H2O and ethyl acetate
3. 3
   Extractionthe aqueous layer was extracted twice with ethyl acetate
4. 4
   DryingThe combined extracts were dried over MgSO4
5. 5
   Filtrationfiltered
6. 6
   Concentrationconcentrated
7. 7
   OtherThe crude product was purified by column chromatography
8. 8
   Washeluting with 5-40% ethyl acetate in hexanes

Procedure

2-(2,6-Dimethyl-morpholin-4-yl)-3,4-difluoro-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzaldehyde (16 grams, 41 mmol), 2-iodopyrazine (Aldrich, 6 grams, 29.1 mmol), sodium carbonate (9.3 grams, 87 mmol) and Pd(PPh3)2Cl2 (Aldrich, 0.82 gram, 1.2 mmol) were suspended in a 1:1 mixture of CH3CN/H2O. The reaction mixture was then purged with nitrogen and heated at 85° C. overnight. Upon completion the reaction was partitioned between H2O and ethyl acetate and the aqueous layer was extracted twice with ethyl acetate. The combined extracts were dried over MgSO4, filtered and concentrated. The crude product was purified by column chromatography eluting with 5-40% ethyl acetate in hexanes to obtain 6.6 grams of the desired product. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.19 (d, J=6.2 Hz, 6H), 3.09 (m, 4H), 3.84 (m, 1H), 8.28 (dd, J=8.1, 2.1 Hz, 1H), 8.53 (d, J=2.5 Hz, 1H), 8.66 (dd, J=2.4, 1.7 Hz, 1H), 9.01 (s, 1 H), 10.22 (s, 1H); MS(APCl+) m/z 334 (MH+).

Source