Reaction #47853

Reaction equation

5-Bromo-N-tert-butylthiophene-2-carboxamide

N-cyclopropyl-4-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide

cesium fluoride

1,4-dioxane

→

N-tert-butyl-5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)thiophene-2-carboxamide

Yield 59.1%

Solvents

EtOAc

water

Conditions

Workup

1. 1
   Filtrationfiltered through Celite
2. 2
   Washthe Celite was washed with DCM
3. 3
   OtherThe combined organic solutions were evaporated under reduced pressure
4. 4
   Washwashed with saturated sodium bicarbonate
5. 5
   Dryingdried over MgSO4
6. 6
   OtherThe organic solutions were evaporated under reduced pressure
7. 7
   Otherchromatographed through a Redi-Sep pre-packed silica gel column (40 g)
8. 8
   Washeluting with a gradient of 5% to 95% MeOH in DCM

Procedure

A 15 ml glass microwave reaction vessel was charged with 5-Bromo-N-tert-butylthiophene-2-carboxamide (1.5 g, 5.7 mmol), N-cyclopropyl-4-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide (1.7 g, 5.7 mmol), cesium fluoride (0.63 g, 17 mmol), tetrakis(triphenylphosphine)palladium(0) (0.46 g, 0.40 mmol), 1,4-dioxane (4 ml, 57 mmol) and water (4 ml). The reaction mixture was heated in a Smith Synthesizer microwave reactor (Personal Chemistry, Inc., Upssala, Sweden) at 150° C. for 20 min. The reaction mixture was diluted with EtOAc and filtered through Celite and the Celite was washed with DCM. The combined organic solutions were evaporated under reduced pressure. The crude residue was suspended in DCM and washed with saturated sodium bicarbonate followed by brine, water and dried over MgSO4. The organic solutions were evaporated under reduced pressure and the crude product was adsorbed onto a plug of silica gel and chromatographed through a Redi-Sep pre-packed silica gel column (40 g), eluting with a gradient of 5% to 95% MeOH in DCM to provide N-tert-butyl-5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)thiophene-2-carboxamide (1.2 g). MS (ES+): 357 (M+H)+.

Source