4-Chlorobenzoic Acid → 4-Chloro-N-(1,1-dimethylethyl)benzamide

HRID 2357511Notes

Reaction equation

HRID 2357511 reaction equation
[Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[CH:4][CH:3]=1.C(Cl)(=O)C(Cl)=O.[C:17]([NH2:21])([CH3:20])([CH3:19])[CH3:18].C([O-])(O)=O.[Na+]>C1(C)C=CC=CC=1.C(OCC)(=O)C.CN(C=O)C>[C:17]([NH:21][C:6](=[O:8])[C:5]1[CH:4]=[CH:3][C:2]([Cl:1])=[CH:10][CH:9]=1)([CH3:20])([CH3:19])[CH3:18]

Participants

8

Reactant 4

HCID 63184-Chlorobenzoic AcidHCID 6385Tert-ButylamineHCID 65578Oxalyl chlorideHCID 516892Sodium Bicarbonate

Product 1

HCID 5873474-Chloro-N-(1,1-dimethylethyl)benzamideYield 84%

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

To a stirred suspension of 4-chlorobenzoic acid (31.3 g, 200 mmol) in toluene (200 mL) was added oxalyl chloride (30 mL, 350 mmol) followed by DMF (0.1 mL). The resulting suspension was heated at reflux until all solids dissolved. The solvent was removed under reduced pressure by rotary evaporation. The resulting semi-solid residue was dissolved in ethyl acetate (200 mL) and cooled in an ice bath under nitrogen with mechanical stirring. A solution of tert-butylamine (53 mL, 500 mmol) in ethyl acetate (50 mL) was carefully added to the mixture dropwise keeping the internal temperature below 10° C. During addition the initially clear solution became thick colorless slurry. Ethyl acetate (50 mL) was added followed by sat. aq. NaHCO3 (300 mL) and the resulting mixture was stirred until two clear layers resulted. The biphasic mixture was transferred into a separatory funnel, and the organic layer was separated. The organic layer was then washed with water (100 mL), brine (100 mL), and dried over anhydrous Na2SO4. Recrystallization from ethyl acetate/hexanes afforded N-tert-butyl-4-chlorobenzamide (35.5 g, 84% yield) as colorless needles (mp 136-137° C.).

Workup

  1. temperatureThe resulting suspension was heated
  2. temperatureat reflux until all solids
  3. dissolutiondissolved
  4. customThe solvent was removed under reduced pressure by rotary evaporation
  5. dissolutionThe resulting semi-solid residue was dissolved in ethyl acetate (200 mL)
  6. temperaturecooled in an ice bath under nitrogen with mechanical stirring
  7. customthe internal temperature below 10° C
  8. additionDuring addition the initially clear solution
  9. customresulted
  10. customThe biphasic mixture was transferred into a separatory funnel
  11. customthe organic layer was separated
  12. washThe organic layer was then washed with water (100 mL), brine (100 mL)
  13. dry with materialdried over anhydrous Na2SO4
  14. customRecrystallization from ethyl acetate/hexanes

Sources & evidence

ORD record
ord-4429274c30744b51ab892d2ddc6bafcb
Source dataset
uspto-grants-2010_07
Patent number
US07759337B2

Reaction notes

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