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

HRID 570133Notes

Reaction equation

HRID 570133 reaction equation
Br[C:2]1[C:3]([C:12]2[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=2)=[N:4][N:5]2[CH:10]([CH3:11])[CH2:9][CH2:8][O:7][C:6]=12.C([B:22]1[O:26][C:25]([CH3:28])([CH3:27])[C:24]([CH3:30])([CH3:29])[O:23]1)(C)C>C1COCC1>[F:18][C:15]1[CH:16]=[CH:17][C:12]([C:3]2[C:2]([B:22]3[O:26][C:25]([CH3:28])([CH3:27])[C:24]([CH3:30])([CH3:29])[O:23]3)=[C:6]3[O:7][CH2:8][CH2:9][CH:10]([CH3:11])[N:5]3[N:4]=2)=[CH:13][CH:14]=1

Participants

4

Reactant 2

HCID 127277112-Isopropyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 894883373-bromo-2-(4-fluorophenyl)-7-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine

Product 1

HCID 894883172-(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]oxazineYield 44%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

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.

Workup

  1. stirringthe reaction mixture is stirred for 2 hours at −78° C
  2. customThen the reaction mixture is quenched by the addition of an aqueous solution of NH4Cl
  3. extractionis extracted with EtOAc
  4. washThe combined organic phases are washed with water and brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated in vacuo
  7. customThe crude is purified by silica gel chromatography (eluent cyclohexane/ethyl acetate)

Sources & evidence

ORD record
ord-8d8bcafc50b3417db0fb46c9e54935ed
Source dataset
uspto-grants-2015_05
Patent number
US09023844B2

Reaction notes

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