3-Buten-2-ol → HCID 89922494, compound

HRID 921924Notes

Reaction equation

HRID 921924 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].[CH3:12][CH:13]([OH:16])[CH:14]=[CH2:15].C1(N(C)C2CCCCC2)CCCCC1>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].C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1C)(C)(C)C.CC#N>[NH2:1][C:2]1[C:3]([Cl:11])=[CH:4][C:5]([CH2:15][CH2:14][C:13](=[O:16])[CH3:12])=[C:6]([CH:9]=1)[C:7]#[N:8]

Participants

7

Reactant 3

HCID 117163-Buten-2-olHCID 24210N-Methyl dicyclohexylamineHCID 532162295-Amino-2-bromo-4-chlorobenzonitrile

Product 1

HCID 89922494HCID 89922494, compoundYield 60%

Reagents, catalysts & solvents 3

HCID 27349372-(Di-tert-butylphosphino)-2'-methyl-1,1'-biphenylCatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
90 °C

Procedure

5-amino-2-bromo-4-chlorobenzonitrile (1.1 g, 4.75 mmol), but-3-en-2-ol (0.445 g, 6.18 mmol), Pd2(dba)3 (0.044 g, 0.048 mmol), di-tert-butyl(2′-methyl-[1,1′-biphenyl]-2-yl)phosphine (0.045 g, 0.143 mmol), and N-cyclohexyl-N-methylcyclohexanamine (1.392 g, 7.13 mmol) were combined in a 20 dram vial and CH3CN (8 mL) was added. The vial was evacuated and backfilled with Ar 4×, and the reaction was heated at 90° C. for 45 min. The reaction was cooled to room temperature and diluted with water, extracting 3× with EtOAc. The organic layers were dried over Na2SO4, filtered, and concentrated in vacuo. The material was then purified by flash column chromatography (0-70% EtOAc/Hex; 80 g column). 5-amino-4-chloro-2-(3-oxobutyl)benzonitrile (635 mg) was obtained as yellow foam.

Workup

  1. customThe vial was evacuated
  2. temperatureThe reaction was cooled to room temperature
  3. additiondiluted with water
  4. extractionextracting 3× with EtOAc
  5. dry with materialThe organic layers were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe material was then purified by flash column chromatography (0-70% EtOAc/Hex; 80 g column)

Sources & evidence

ORD record
ord-ccd25bae8f4948bd9004b0acde0298af
Source dataset
uspto-grants-2016_03
Patent number
US09273057B2

Reaction notes

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