4,4,5,5-Tetramethyl-2-(prop-1-en-2-yl)-1,3,2-dioxaborolane → 8-Fluoro-2-isopropenyl-4-methyl-3-(4-pyrazol-1-ylbenzyl)quinolin-5-ol

HRID 1944363Notes

Reaction equation

HRID 1944363 reaction equation
Cl[C:2]1[C:11]([CH2:12][C:13]2[CH:18]=[CH:17][C:16]([N:19]3[CH:23]=[CH:22][CH:21]=[N:20]3)=[CH:15][CH:14]=2)=[C:10]([CH3:24])[C:9]2[C:8]([OH:25])=[CH:7][CH:6]=[C:5]([F:26])[C:4]=2[N:3]=1.[C:27](B1OC(C)(C)C(C)(C)O1)([CH3:29])=[CH2:28].O.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>CN(C)C=O>[F:26][C:5]1[C:4]2[N:3]=[C:2]([C:27]([CH3:29])=[CH2:28])[C:11]([CH2:12][C:13]3[CH:18]=[CH:17][C:16]([N:19]4[CH:23]=[CH:22][CH:21]=[N:20]4)=[CH:15][CH:14]=3)=[C:10]([CH3:24])[C:9]=2[C:8]([OH:25])=[CH:7][CH:6]=1

Participants

5

Reactant 3

HCID 109974264,4,5,5-Tetramethyl-2-(prop-1-en-2-yl)-1,3,2-dioxaborolaneHCID 22031701Potassium phosphate, tribasic, monohydrateHCID 1363483602-Chloro-8-fluoro-4-methyl-3-(4-pyrazol-1-ylbenzyl)quinolin-5-ol

Product 1

HCID 1363483598-Fluoro-2-isopropenyl-4-methyl-3-(4-pyrazol-1-ylbenzyl)quinolin-5-ol

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 2-chloro-8-fluoro-4-methyl-3-(4-pyrazol-1-ylbenzyl)quinolin-5-ol (0.22 g), 2-isopropenyl-4,4,5,5-tetramethyl[1,3,2]dioxaborolane (0.23 mL), potassium phosphate monohydrate (0.68 g) and N,N-dimethylformamide (3.0 mL) was purged with argon for 20 minutes, and then treated with [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium (II) (0.048 g), and the mixture heated at 90° C. for 12 hours. The mixture was cooled to room temperature, filtered through Celite and concentrated under reduced pressure. The residue was diluted with saturated aqueous ammonium chloride solution (50 mL) and extracted with ethyl acetate (3×20 mL). The combined extracts were washed with water (5.0 mL) and saturated aqueous sodium chloride solution (5.0 mL), dried over magnesium sulfate and concentrated under reduced pressure. Purification of the residue by column chromatography on silica gel, eluting with a mixture of cyclohexane and ethyl acetate (1:0 to 1:1 by volume) gave title compound as a white solid (0.082 g).

Workup

  1. customwas purged with argon for 20 minutes
  2. additiontreated with [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium (II) (0.048 g)
  3. temperatureThe mixture was cooled to room temperature
  4. filtrationfiltered through Celite
  5. concentrationconcentrated under reduced pressure
  6. additionThe residue was diluted with saturated aqueous ammonium chloride solution (50 mL)
  7. extractionextracted with ethyl acetate (3×20 mL)
  8. washThe combined extracts were washed with water (5.0 mL) and saturated aqueous sodium chloride solution (5.0 mL)
  9. dry with materialdried over magnesium sulfate
  10. concentrationconcentrated under reduced pressure
  11. customPurification of the residue by column chromatography on silica gel
  12. washeluting with a mixture of cyclohexane and ethyl acetate (1:0 to 1:1 by volume)

Sources & evidence

ORD record
ord-a0404fb267204695bd0bd00cf2ebb2fb
Source dataset
uspto-grants-2013_03
Patent number
US08394830B2

Reaction notes

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