Potassium Acetate → ethyl 5-(2-fluoro-4-(2-methoxy-4,6-dimethylpyridin-3-yl)phenyl)-1-[(3RS,4SR)-4-hydroxytetrahydrofuran-3-yl]-1H-pyrazole-4-carboxylate

HRID 1043967Notes

Reaction equation

HRID 1043967 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]([CH:13]3[CH:17]([OH:18])[CH2:16][O:15][CH2:14]3)[N:11]=[CH:10][C:9]=2[C:19]([O:21][CH2:22][CH3:23])=[O:20])=[C:4]([F:24])[CH:3]=1.B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.C([O-])(=O)C.[K+].Br[C:49]1[C:50]([O:57][CH3:58])=[N:51][C:52]([CH3:56])=[CH:53][C:54]=1[CH3:55]>CN(C=O)C.O>[F:24][C:4]1[CH:3]=[C:2]([C:49]2[C:50]([O:57][CH3:58])=[N:51][C:52]([CH3:56])=[CH:53][C:54]=2[CH3:55])[CH:7]=[CH:6][C:5]=1[C:8]1[N:12]([CH:13]2[CH:17]([OH:18])[CH2:16][O:15][CH2:14]2)[N:11]=[CH:10][C:9]=1[C:19]([O:21][CH2:22][CH3:23])=[O:20]

Participants

7

Reactant 4

HCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 866863313-Bromo-2-methoxy-4,6-dimethylpyridineHCID 86686403Ethyl 5-(4-bromo-2-fluorophenyl)-1-[(3RS,4SR)-4-hydroxytetrahydrofuran-3-yl]-1H-pyrazole-4-carboxylate

Product 1

HCID 86686402ethyl 5-(2-fluoro-4-(2-methoxy-4,6-dimethylpyridin-3-yl)phenyl)-1-[(3RS,4SR)-4-hydroxytetrahydrofuran-3-yl]-1H-pyrazole-4-carboxylate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
90 °C

Procedure

Ethyl 5-(4-bromo-2-fluorophenyl)-1-[(3RS,4SR)-4-hydroxytetrahydrofuran-3-yl]-1H-pyrazole-4-carboxylate (3.8 g), bis(pinacolato)diboron (2.90 g), potassium acetate (2.80 g) and Pd(dppf)Cl2-DCM complex (480 mg) were added to DMF (38.3 mL), and the mixture was stirred at 90° C. in a nitrogen atmosphere. After stirring the reaction mixture for about two hours, a solution of 3-bromo-2-methoxy-4,6-dimethylpyridine obtained in Preparation Example 26 (3.09 g) in DMF (15 mL), and water (22 mL) were added, and the mixture was warmed to 120° C. and further stirred for about five hours. The reaction mixture was cooled to room temperature and concentrated under reduced pressure, and the residue was passed through a silica gel pad (NH silica gel, eluting with ethyl acetate). The filtrate was concentrated to about 200 mL and then partitioned by adding brine. The organic layer was dried over anhydrous magnesium sulfate and filtered. The filtrate was concentrated, and the residue was purified by NH silica gel column chromatography (ethyl acetate/n-heptane, 70% to 90%) to give the title compound (2.26 g).

Workup

  1. stirringAfter stirring the reaction mixture for about two hours
  2. additionwere added
  3. temperaturethe mixture was warmed to 120° C.
  4. stirringfurther stirred for about five hours
  5. temperatureThe reaction mixture was cooled to room temperature
  6. concentrationconcentrated under reduced pressure
  7. washthe residue was passed through a silica gel pad (NH silica gel, eluting with ethyl acetate)
  8. concentrationThe filtrate was concentrated to about 200 mL
  9. custompartitioned
  10. additionby adding brine
  11. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  12. filtrationfiltered
  13. concentrationThe filtrate was concentrated
  14. customthe residue was purified by NH silica gel column chromatography (ethyl acetate/n-heptane, 70% to 90%)

Sources & evidence

ORD record
ord-33eff9c85f6a43cc8dd0b8e48704f6a8
Source dataset
uspto-grants-2013_10
Patent number
US08563565B2

Reaction notes

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