Hexanal → HCID 17972745, compound

HRID 1372499Notes

Reaction equation

HRID 1372499 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:14])[C:10]([CH3:13])([CH3:12])[CH3:11])=[C:4]([F:15])[CH:3]=1.C([Li])CCC.[CH:21](=[O:27])[CH2:22][CH2:23][CH2:24][CH2:25][CH3:26]>O1CCCC1>[F:15][C:4]1[CH:3]=[C:2]([CH:21]([OH:27])[CH2:22][CH2:23][CH2:24][CH2:25][CH3:26])[CH:7]=[CH:6][C:5]=1[NH:8][C:9](=[O:14])[C:10]([CH3:13])([CH3:12])[CH3:11]

Participants

5

Reactant 3

HCID 6184HexanalHCID 4149902N-(4-bromo-2-fluorophenyl)-2,2-dimethylpropanamideHCID 178418339Butyllithium

Product 1

HCID 17972745HCID 17972745, compoundYield 76%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

A solution of N-(4-bromo-2-fluorophenyl)-2,2-dimethylpropanamide (22.6 g, 82.5 mmol) in anhydrous tetrahydrofuran (410 mL) was placed under a nitrogen atmosphere, cooled in a dry ice-acetone bath, and stirred while butyllithium (83 mL of a 2.5M solution in hexanes, 207.5 mmol) was added dropwise by syringe pump over 2.5 hours. The resulting mixture was aged at −78° C. for 30 minutes and then treated with hexanal (25 mL, 208 mmol) added dropwise by syringe pump over 135 minutes. After stirring at −78° C. for an additional 70 minutes, the mixture was removed from the cooling bath, treated with aqueous 50% saturated NH4Cl, and the layers separated. The aqueous portion was extracted with EtOAc. The combined organics were washed with aqueous NaHCO3 and brine, dried over MgSO4, filtered, and concentrated under vacuum to an oil. The crude product was purified by flash chromatography on a Biotage 75 L KP-Sil column, eluting with 4:1 hexanes-EtOAc (25×400 mL fractions). Fractions 9–22 were combined and evaporated under vacuum to afford N-[2-fluoro-4-(1-hydroxyhexyl)phenyl]-2,2-dimethylpropanamide (18.5 g, 76%) as a clear oil.

Workup

  1. temperaturecooled in a dry ice-acetone bath
  2. additionwas added dropwise by syringe pump over 2.5 hours
  3. additionadded dropwise by syringe pump over 135 minutes
  4. customthe mixture was removed from the cooling bath
  5. additiontreated with aqueous 50% saturated NH4Cl
  6. customthe layers separated
  7. extractionThe aqueous portion was extracted with EtOAc
  8. washThe combined organics were washed with aqueous NaHCO3 and brine
  9. dry with materialdried over MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated under vacuum to an oil
  12. customThe crude product was purified by flash chromatography on a Biotage 75 L KP-Sil column
  13. washeluting with 4:1 hexanes-EtOAc (25×400 mL fractions)
  14. customevaporated under vacuum

Sources & evidence

ORD record
ord-e34f216f285d480d8e0355ec6d3ee6ed
Source dataset
uspto-grants-2007_01
Patent number
US07157604B2

Reaction notes

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