2,2,2'-Trimethylpropionanilide → HCID 19096192, compound

HRID 486660Notes

Reaction equation

HRID 486660 reaction equation
[CH3:1][C:2]([CH3:14])([CH3:13])[C:3]([NH:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[CH3:12])=[O:4].C([Li])CCC.[CH3:20][N:21]=[CH:22][C:23]1[CH:27]=[CH:26][S:25][CH:24]=1>O1CCCC1.CCCCCC.C1(C)C=CC=CC=1>[CH3:20][NH:21][CH:22]([C:23]1[CH:27]=[CH:26][S:25][CH:24]=1)[CH2:12][C:7]1[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=1[NH:5][C:3](=[O:4])[C:2]([CH3:14])([CH3:13])[CH3:1]

Participants

7

Reactant 3

HCID 27340052,2,2'-TrimethylpropionanilideHCID 11829437124416-00-82×HCID 178418339Butyllithium

Product 1

HCID 19096192HCID 19096192, compoundYield 56.9%

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent

Conditions

Temperature
0 °C

Procedure

To a chilled, solution (-50° C.) of 19.13 g of 2,2-dimethyl-N-[(2-methyl)phenyl]propanamide in 200 ml of tetrahydrofuran was added, dropwise over 1.5 hours, 88 ml of a 2.5M solution of n-butyllithium in hexane. Upon completion of the addition, the resultant solution was stirred for 2 hours with cooling. A solution of 15.0 g of 3-thiophene-carboxaldehyde methylimine in 30 ml of toluene, was then added, dropwise over 15 minutes, to the cooled solution. Upon completion of the 3-thiophenecarboxaldehyde methylimine addition, the reaction mixture was stirred for 20 minutes at 0° C., quenched by the addition of 300 ml of water, concentrated, and extracted with dichloromethane. The combined extract was dried over anhydrous magnesium sulfate, filtered, and concentrated to an oil. HPLC of the oil (Water's Associates Prep LC/System 500; silica gel; methanol as the eluent) afforded a semipurified product which was subsequently chromatographed under otherwise identical conditions utilizing ethyl acetate, followed by methanol as eluents. Concentration of the appropriate fractions and trituration with hexane yielded 18.0 g of N-[2-[2-(methylamino)-2-(3-thienyl)ethyl]phenyl]-2,2-dimethylpropanamide. mp 81°-84° C.

Workup

  1. additionUpon completion of the addition
  2. temperaturewith cooling
  3. customquenched by the addition of 300 ml of water
  4. concentrationconcentrated
  5. extractionextracted with dichloromethane
  6. extractionThe combined extract
  7. dry with materialwas dried over anhydrous magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated to an oil
  10. custommethanol as the eluent) afforded a semipurified product which
  11. customwas subsequently chromatographed under otherwise identical conditions

Sources & evidence

ORD record
ord-d02957419c5f418088e72cf8039da091
Source dataset
uspto-grants-1994_03
Patent number
US05292760

Reaction notes

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