Methyl iodide → rac-2-[(Diphenylmethylene)amino]-4-fluoro-2-methylbutanonitrile

HRID 1486269Notes

Reaction equation

HRID 1486269 reaction equation
[C:1]1([C:7](=[N:14][CH:15]([CH2:18][CH2:19][F:20])[C:16]#[N:17])[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH2:21]([Li])CCC.IC>C1COCC1>[C:1]1([C:7](=[N:14][C:15]([CH3:21])([CH2:18][CH2:19][F:20])[C:16]#[N:17])[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 117858214rac-2-[(Diphenylmethylene)amino]-4-fluorobutanonitrileHCID 178418339Butyllithium

Product 1

HCID 90251299rac-2-[(Diphenylmethylene)amino]-4-fluoro-2-methylbutanonitrileYield 96.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

19.94 g (63.64 mmol, 85% purity) of rac-2-[(diphenylmethylene)amino]-4-fluorobutanonitrile from Example 66A were initially charged in 421 ml of abs. THF, and 25.71 ml (64.28 mmol) of n-butyllithium (2.5 N in hexane) were added at −78° C. under argon, and the mixture was stirred at −78° C. for a further 10 min. Subsequently, 36.1 g (254.57 mmol) of iodomethane were added to the reaction solution at −78° C. The reaction mixture was gradually brought to 0° C. over 4.5 h. After complete depletion of the starting material, the reaction solution was quenched with water at 0° C., ethyl acetate was added and the mixture was washed twice with saturated aqueous sodium chloride solution. The organic phase was dried over sodium sulphate, filtered and concentrated by rotary evaporation. The residue was purified by means of silica gel chromatography (eluent:cyclohexane/ethyl acetate=15/1). 17.2 g of the target compound were obtained (78% of theory, 81% purity).

Workup

  1. waitThe reaction mixture was gradually brought to 0° C. over 4.5 h
  2. customAfter complete depletion of the starting material, the reaction solution was quenched with water at 0° C.
  3. additionethyl acetate was added
  4. washthe mixture was washed twice with saturated aqueous sodium chloride solution
  5. dry with materialThe organic phase was dried over sodium sulphate
  6. filtrationfiltered
  7. concentrationconcentrated by rotary evaporation
  8. customThe residue was purified by means of silica gel chromatography (eluent:cyclohexane/ethyl acetate=15/1)

Sources & evidence

ORD record
ord-2bb6adae56564755ae51aabcc8900153
Source dataset
uspto-grants-2016_08
Patent number
US09422285B2

Reaction notes

Loading…