Toluene → HCID 57437656, compound

HRID 338183Notes

Reaction equation

HRID 338183 reaction equation
O1CCCOB1[C:7]1[CH:14]=[CH:13][CH:12]=[CH:11][C:8]=1[C:9]#[N:10].Br[C:16]1[CH:22]=[C:21]([C:23]([CH3:26])([CH3:25])[CH3:24])[CH:20]=[CH:19][C:17]=1[NH2:18].C([O-])([O-])=O.[K+].[K+].C1(C)C=CC=CC=1>[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(O)C>[C:23]([C:21]1[CH:22]=[CH:16][C:17]2[C:19](=[C:7]3[C:8](=[C:9]([NH2:10])[N:18]=2)[CH:11]=[CH:12][CH:13]=[CH:14]3)[CH:20]=1)([CH3:26])([CH3:24])[CH3:25]

Participants

7

Reactant 4

HCID 1140TolueneHCID 11430Potassium CarbonateHCID 2385912-Bromo-4-(tert-butyl)anilineHCID 35296022-(1,3,2-Dioxaborinan-2-yl)benzonitrile

Product 1

HCID 57437656HCID 57437656, compoundYield 35.5%

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 702EthanolSolvent

Procedure

35.7 g (190 mmol) 2-(1,3,2-dioxaborinan-2-yl)benzonitrile, 31.9 g (158 mmol) 2-bromo-4-(tertbutyl)aniline, 3.6 g (3.16 mmol) tetrakis(triphenylphosphine) palladium(0) and 59.0 g (427 mmol) K2CO3 were heated to reflux in a 2 L flask containing 400 ml toluene and 300 mL ethanol. The reaction mixture was heated for 19 hours under constant N2 purge. HPLC of the reaction mixture indicated consumption of the starting aniline. The mixture was cooled and then filtered to remove the base. The base was washed with EtOAc to remove trace organic. The combined filtrate was evaporated down to give impure oil. The oil was purified on a column of silica using 95/5/0.05 CH2Cl2/MeOH/NH4OH as eluent to obtain separation. The product fractions were evaporated of solvent and the resultant residue recrystallized from CH2Cl2/hexanes to yield 14.0 g of the target compound as white solids (35.5% yield, confirmed by GC-MS).

Workup

  1. temperatureto reflux in a 2 L flask
  2. temperatureThe reaction mixture was heated for 19 hours under constant N2
  3. custompurge
  4. customconsumption of the starting aniline
  5. temperatureThe mixture was cooled
  6. filtrationfiltered
  7. customto remove the base
  8. washThe base was washed with EtOAc
  9. customto remove trace organic
  10. customThe combined filtrate was evaporated down
  11. customto give impure oil
  12. customThe oil was purified on a column of silica using 95/5/0.05 CH2Cl2/MeOH/NH4OH as eluent
  13. customto obtain
  14. customseparation
  15. customThe product fractions were evaporated of solvent
  16. customthe resultant residue recrystallized from CH2Cl2/hexanes

Sources & evidence

ORD record
ord-b5e1aadfa544403fbd279dcb5c764c14
Source dataset
uspto-grants-2014_11
Patent number
US08889864B2

Reaction notes

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