4-Bromo-1,2-dichlorobenzene → HCID 18327742, compound

HRID 1250252Notes

Reaction equation

HRID 1250252 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([Cl:8])=[C:4]([Cl:9])[CH:3]=1.[CH3:10][N:11]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH:12]([CH2:14][CH:15]=[CH2:16])[CH3:13]>O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C(#N)C.C(N(CC)CC)C.CCOC(C)=O.CCCCCC>[CH3:10][N:11]([C:17]([O:19][C:20]([CH3:21])([CH3:23])[CH3:22])=[O:18])[CH:12]([CH2:14]/[CH:15]=[CH:16]/[C:2]1[CH:7]=[CH:6][C:5]([Cl:8])=[C:4]([Cl:9])[CH:3]=1)[CH3:13]

Participants

9

Reactant 2

HCID 290134-Bromo-1,2-dichlorobenzeneHCID 15546849N-methyl-N-(tert-butoxycarbonyl)-4-penten-2-amine

Product 1

HCID 18327742HCID 18327742, compoundYield 101.6%

Reagents, catalysts & solvents 6

HCID 80271Tri-o-tolylphosphineCatalyst2×HCID 167845palladium(II) acetateCatalyst2×HCID 962WaterSolventHCID 6342AcetonitrileSolvent2×HCID 8471TriethylamineSolvent2×HCID 21226206Ethyl acetate hexaneSolvent

Conditions

Temperature
85 °C

Procedure

Under a nitrogen atmosphere, a mixture of 4-bromo-1,2-dichlorobenzene (1.81 g, 8.03 mmol), N-methyl-N-(tert-butoxycarbonyl)-4-penten-2-amine (1.60 g, 8.03 mmol), prepared as previously described, palladium(II) acetate (18.0 mg, 0.08 mmol), tri-o-tolylphosphine (97.7 mg, 0.32 mmol), triethylamine (2.5 mL, 17.94 mmol) and anhydrous acetonitrile (5 mL) was stirred and heated under reflux at 80-90° C. (oil bath temperature) for 18 h. TLC analysis on silica gel eluting with EtOAc-hexane (3:1, v/v) indicated an incomplete reaction. Therefore, additional palladium(II) acetate (18.0 mg), tri-o-tolylphosphine (92 mg), triethylamine (2.5 mL) and anhydrous acetonitrile (5 mL) were added and heating was continued at 60° C. for an additional 40 h. The resulting mixture, an oily brown semi-solid, was cooled to ambient temperature, diluted with water (25 mL), and extracted with CH2Cl2 (3×25 mL). The combined CH2Cl2 extracts were dried (Na2SO4), filtered, concentrated by rotary evaporation, and the residue was dried under high vacuum to produce a dark-brown oil (2.81 g). The crude product was purified by column chromatography on silica gel (132 g), eluting with ethyl acetate-hexane (15:85, v/v). Selected fractions containing the product (Rf 0.34) were combined, concentrated by rotary evaporation and the residue was vacuum dried to give 1.38 g (50.0%) of a light-yellow oil.

Workup

  1. customprepared
  2. temperatureheated
  3. customan incomplete reaction
  4. temperatureheating
  5. temperatureThe resulting mixture, an oily brown semi-solid, was cooled to ambient temperature
  6. extractionextracted with CH2Cl2 (3×25 mL)
  7. dry with materialThe combined CH2Cl2 extracts were dried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated by rotary evaporation
  10. customthe residue was dried under high vacuum

Sources & evidence

ORD record
ord-2e6382559e0845068874454b342d49e5
Source dataset
uspto-grants-2002_01
Patent number
US06337351B1

Reaction notes

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