Bromide ion → HCID 59632303, compound

HRID 2369095Notes

Reaction equation

HRID 2369095 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]([C:13]3[C:18]([Cl:19])=[CH:17][CH:16]=[CH:15][C:14]=3[Cl:20])[N:11]=[C:10]([C:21]([OH:24])([CH3:23])[CH3:22])[CH:9]=2)=[C:4]([CH3:25])[CH:3]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].C([Li])CCC.[Br-].C1C[O:45][CH2:44]C1>CCOCC.CCCCCC.CN(C=O)C>[Cl:20][C:14]1[CH:15]=[CH:16][CH:17]=[C:18]([Cl:19])[C:13]=1[N:12]1[C:8]([C:5]2[CH:6]=[CH:7][C:2]([CH:44]=[O:45])=[CH:3][C:4]=2[CH3:25])=[CH:9][C:10]([C:21]([OH:24])([CH3:23])[CH3:22])=[N:11]1

Participants

9

Reactant 5

HCID 259Bromide ionHCID 8028Tetrahydrofuran2×HCID 2733832Lithium HexamethyldisilazideHCID 59632125HCID 59632125, compoundHCID 178418339Butyllithium2×

Product 1

HCID 59632303HCID 59632303, compound

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent2×HCID 8058HexaneSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a cold (−78° C.) solution of 2-(5-(4-bromo-2-methylphenyl)-1-(2,6-dichlorophenyl)-1H-pyrazol-3-yl)propan-2-ol (215 mg, 0.49 mmol) in a mixture of THF (4 mL) and Et2O (4 mL) was added lithium bis(trimethylsilyl)amide (0.5 mL of a 1.0M solution in THF, 0.5 mmol). After several minutes stirring at −78° C. the resulting alkoxide solution was treated with n-butyllithium (1.0 mL of a 1.6M solution in hexane, 1.6 mmol). After 10 minutes stirring at −78° C., LC/MS showed some starting bromide present in a quenched aliquot of the reaction. After 30 minutes additional n-butyllithium was added (0.5 mL of a 1.6M solution in hexane, 0.8 mmol). After an additional 15 minutes stirring at −78° C. the reaction mixture was treated with dry N,N-dimethylformamide (0.4 mL, 5.2 mmol). Several minutes after the addition of the DMF, the −78° C. bath was replaced with an ice bath and the reaction mixture was allowed to come to ambient temperature overnight. The reaction was quenched by the addition of saturated NH4Cl and diluted with EtOAc. The layers were separated and the aqueous was extracted with EtOAc (3×). Combined organic extracts were washed with brine, dried (Na2SO4), filtered and concentrated under reduced pressure to afford a yellow syrup. The crude product was purified by flash column chromatography eluting with 0% to 100% EtOAc/hexane to afford 4-(1-(2,6-dichlorophenyl)-3-(2-hydroxypropan-2-yl)-1H-pyrazol-5-yl)-3-methylbenzaldehyde which was carried on to the next step without further purification. MS(ES): 389 [M+H]+.

Workup

  1. custompresent in a quenched aliquot of the reaction
  2. stirringAfter an additional 15 minutes stirring at −78° C. the reaction mixture
  3. customthe −78° C. bath was replaced with an ice bath
  4. waitto come to ambient temperature overnight
  5. customThe reaction was quenched by the addition of saturated NH4Cl
  6. additiondiluted with EtOAc
  7. customThe layers were separated
  8. extractionthe aqueous was extracted with EtOAc (3×)
  9. washCombined organic extracts were washed with brine
  10. dry with materialdried (Na2SO4)
  11. filtrationfiltered
  12. concentrationconcentrated under reduced pressure
  13. customto afford a yellow syrup
  14. customThe crude product was purified by flash column chromatography
  15. washeluting with 0% to 100% EtOAc/hexane

Sources & evidence

ORD record
ord-2e650c33d59e44a7bd796abcd3381fe0
Source dataset
uspto-grants-2014_04
Patent number
US08703805B2

Reaction notes

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