N-Methyl dicyclohexylamine → HCID 89922748, compound

HRID 921840Notes

Reaction equation

HRID 921840 reaction equation
[NH2:1][C:2]1[C:3]([Cl:11])=[CH:4][C:5](Br)=[C:6]([CH:9]=1)[C:7]#[N:8].C1(N(C)C2CCCCC2)CCCCC1.C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1C)(C)(C)C.[CH2:48]([OH:52])[CH2:49][CH:50]=[CH2:51]>CC#N.O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CN(C=O)C>[NH2:1][C:2]1[C:3]([Cl:11])=[CH:4][C:5]([CH2:51][CH2:50][CH2:49][CH:48]=[O:52])=[C:6]([CH:9]=1)[C:7]#[N:8]

Participants

9

Reactant 4

HCID 24210N-Methyl dicyclohexylamineHCID 693893-Buten-1-olHCID 27349372-(Di-tert-butylphosphino)-2'-methyl-1,1'-biphenylHCID 532162295-Amino-2-bromo-4-chlorobenzonitrile

Product 1

HCID 89922748HCID 89922748, compoundYield 23.4%

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
60 °C

Procedure

5-amino-2-bromo-4-chlorobenzonitrile (4 g, 17.28 mmol) and N-cyclohexyl-N-methylcyclohexanamine (5.55 mL, 25.9 mmol) were combined in a 250 ml flask and 2 ml of DMF was added. The flask was evacuated and backfilled with Ar 4×. A suspension of Pd2 (dba)3 (0.316 g, 0.346 mmol) and di-tert-butyl(2′-methyl-[1,1′-biphenyl]-2-yl)phosphine (0.324 g, 1.037 mmol) in CH3CN (32 mL) was heated at 60° C. for 1 min until the solids dissolved and then cooled to room temperature. The solution was added to the flask by syringe, and then but-3-en-1-ol (1.933 mL, 22.46 mmol) was added. The reaction was heated at 90° C. for 45 min. The reaction was cooled to room temperature and diluted with H2O, extracting 3× with EtOAc. The organic layers were dried over Na2SO4, filtered, and concentrated. The material was purified by flash column chromatography (0-70% EtOAc/Hex; 330 g column). 5-amino-4-chloro-2-(4-oxobutyl)benzonitrile (0.9 g) was obtained as yellow foam.

Workup

  1. customThe flask was evacuated
  2. dissolutiondissolved
  3. temperaturecooled to room temperature
  4. additionThe solution was added to the flask by syringe
  5. temperatureThe reaction was heated at 90° C. for 45 min
  6. temperatureThe reaction was cooled to room temperature
  7. extractionextracting 3× with EtOAc
  8. dry with materialThe organic layers were dried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe material was purified by flash column chromatography (0-70% EtOAc/Hex; 330 g column)

Sources & evidence

ORD record
ord-0f4bb32eddc3463780d0ae6a7a871ff0
Source dataset
uspto-grants-2016_03
Patent number
US09273057B2

Reaction notes

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