Ethyl Acetate → 3-Bromo-5-(dimethylamino)benzonitrile

HRID 2070939Notes

Reaction equation

HRID 2070939 reaction equation
N[C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([Br:10])[CH:9]=1)[C:5]#[N:6].[BH3-][C:12]#[N:13].[Na+].[CH3:15]COC(C)=O.C([O-])(O)=O.[Na+]>CC#N.C=O.O.C(O)(=O)C>[Br:10][C:8]1[CH:7]=[C:4]([CH:3]=[C:2]([N:13]([CH3:12])[CH3:15])[CH:9]=1)[C:5]#[N:6]

Participants

9

Reactant 4

HCID 8857Ethyl AcetateHCID 516892Sodium BicarbonateHCID 5003444Sodium cyanoborohydrideHCID 534069613-Amino-5-bromobenzonitrile

Product 1

HCID 686703103-Bromo-5-(dimethylamino)benzonitrileYield 28%

Reagents, catalysts & solvents 4

HCID 176Acetic AcidCatalyst2×HCID 712FormaldehydeSolventHCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

To a stirring suspension of 210 mg (10.6 mmol) of 3-amino-5-bromobenzonitrile in 11 mL of CH3CN and 11 mL of 37% formaldehyde in H2O was added 222 mg (3.53 mmol) of NaCNBH3 followed by about 7 drops of acetic acid to a pH=7. After 1 h 40 min., an additional amount of acetic acid (10 drops) was added. After 15 h, 40 mL of EtOAc and 40 mL of sat. NaHCO3 was added, and the layers were separated. The organic layer was washed with 25 mL of sat. NaHCO3 and 25 mL of brine, dried over Na2SO4, filtered, and concentrated. Purification by flash silica gel chromatography (10% EtOAc/hexanes) provided 67.4 mg of 3-bromo-5-(dimethylamino)benzonitrile as a yellow solid in 28% yield.

Workup

  1. waitAfter 15 h
  2. customthe layers were separated
  3. washThe organic layer was washed with 25 mL of sat. NaHCO3 and 25 mL of brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification by flash silica gel chromatography (10% EtOAc/hexanes)

Sources & evidence

ORD record
ord-0e30242a83c442ee85cc5085d7e1f08b
Source dataset
uspto-grants-2012_10
Patent number
US08299267B2

Reaction notes

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