N,N-Dimethylhexanamide → N-(2-fluoro-4-hexanoyl-6-methylphenyl)-2,2-dimethylpropanamide

HRID 1372532Notes

Reaction equation

HRID 1372532 reaction equation
Br[C:2]1[CH:7]=[C:6]([CH3:8])[C:5]([NH:9][C:10](=[O:15])[C:11]([CH3:14])([CH3:13])[CH3:12])=[C:4]([F:16])[CH:3]=1.C([Li])CCC.CN(C)[C:24](=[O:30])[CH2:25][CH2:26][CH2:27][CH2:28][CH3:29]>O1CCCC1>[F:16][C:4]1[CH:3]=[C:2]([C:24](=[O:30])[CH2:25][CH2:26][CH2:27][CH2:28][CH3:29])[CH:7]=[C:6]([CH3:8])[C:5]=1[NH:9][C:10](=[O:15])[C:11]([CH3:14])([CH3:13])[CH3:12]

Participants

5

Reactant 3

HCID 22084N,N-DimethylhexanamideHCID 17972716N-(4-Bromo-2-fluoro-6-methylphenyl)pivalamideHCID 178418339Butyllithium

Product 1

HCID 17972706N-(2-fluoro-4-hexanoyl-6-methylphenyl)-2,2-dimethylpropanamideYield 55%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A solution of N-(4-bromo-2-fluoro-6-methylphenyl)-2,2-dimethylpropanamide (21.7 g, 79.2 mmol) in anhydrous tetrahydrofuran (500 mL) was placed under a nitrogen atmosphere, cooled in a dry ice-acetone bath, and stirred while butyllithium (124 mL of a 1.6M solution in hexanes, 198 mmol) was added dropwise. The resulting mixture was aged at −78° C. for 30 minutes and then treated with N,N-dirnethylhexanamide (28.3 g, 198 mmol). After warming up to 0° C. over 2 hours, the mixture was removed from the cooling bath and treated with aqueous saturated NH4Cl (20 mL). The resulting slurry was diluted with CH2Cl2 (1000 mL), dried over MgSO4, filtered through a pad of silica, and concentrated under vacuum. The residue was purified by flash chromatography on a Biotage 40M KP-Sil column, eluting with 19:1 to 9:1 hexanes-EtOAc. The product containing fractions were evaporated under vacuum to provide N-(2-fluoro-4-hexanoyl-6-methylphenyl)-2,2-dimethylpropanamide (12.7 g, 55%) as a yellow foam.

Workup

  1. temperaturecooled in a dry ice-acetone bath
  2. additionwas added dropwise
  3. customthe mixture was removed from the cooling bath
  4. additiontreated with aqueous saturated NH4Cl (20 mL)
  5. additionThe resulting slurry was diluted with CH2Cl2 (1000 mL)
  6. dry with materialdried over MgSO4
  7. filtrationfiltered through a pad of silica
  8. concentrationconcentrated under vacuum
  9. customThe residue was purified by flash chromatography on a Biotage 40M KP-Sil column
  10. washeluting with 19:1 to 9:1 hexanes-EtOAc
  11. additionThe product containing fractions
  12. customwere evaporated under vacuum

Sources & evidence

ORD record
ord-2b291de58e0c4d46b726383f585d3e25
Source dataset
uspto-grants-2007_01
Patent number
US07157604B2

Reaction notes

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