Reaction #657315

Reaction equation

3-bromo-2-(4-fluorophenyl)-7-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine

2-isopropyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

→

2-(4-fluorophenyl)-7-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine

Yield 44.0%

Solvents

THF

THF

Conditions

Workup

1. 1
   workup.STIRRINGthe reaction mixture is stirred for 2 hours at −78° C
2. 2
   OtherThen the reaction mixture is quenched by the addition of an aqueous solution of NH4Cl
3. 3
   Extractionis extracted with EtOAc
4. 4
   WashThe combined organic phases are washed with water and brine
5. 5
   Dryingdried over Na2SO4
6. 6
   Concentrationconcentrated in vacuo
7. 7
   OtherThe crude is purified by silica gel chromatography (eluent cyclohexane/ethyl acetate)

Procedure

To a solution of 3-bromo-2-(4-fluorophenyl)-7-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine (1.5 g, 4.82 mmol, 1 eq) in THF (40 ml) is added a solution of n-Buli (3.314 ml, 1.6 M, 5.30 mmol, 1.1 eq) dropwise at −78° C. After 20 min of stirring, a solution of 1.23 g of 2-isopropyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (7.23 mmol, 1.1 eq) in THF is added dropwise and the reaction mixture is stirred for 2 hours at −78° C. Then the reaction mixture is quenched by the addition of an aqueous solution of NH4Cl and is extracted with EtOAc. The combined organic phases are washed with water and brine, dried over Na2SO4 and concentrated in vacuo. The crude is purified by silica gel chromatography (eluent cyclohexane/ethyl acetate). 760 mg (42%) of 2-(4-fluorophenyl)-7-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine are obtained.

Source