N-Methylphthalimide → alpha-(1-hydroxy-2-methyl-3-oxoisoindolin-1-yl)-N-methyl-o-toluamide

HRID 2419645Notes

Reaction equation

HRID 2419645 reaction equation
[CH3:1][NH:2][C:3]([C:5]1[C:6]([CH3:11])=[CH:7][CH:8]=[CH:9][CH:10]=1)=[O:4].C([Li])CCC.[CH3:17][N:18]1[C:22](=[O:23])[C:21]2=[CH:24][CH:25]=[CH:26][CH:27]=[C:20]2[C:19]1=[O:28]>O1CCCC1.CCCCCC>[OH:23][C:22]1([CH2:11][C:6]2[C:5]([C:3]([NH:2][CH3:1])=[O:4])=[CH:10][CH:9]=[CH:8][CH:7]=2)[C:21]2[C:20](=[CH:27][CH:26]=[CH:25][CH:24]=2)[C:19](=[O:28])[N:18]1[CH3:17]

Participants

6

Reactant 3

HCID 11074N-MethylphthalimideHCID 75111N-methyl-2-toluamideHCID 178418339Butyllithium

Product 1

HCID 20314321alpha-(1-hydroxy-2-methyl-3-oxoisoindolin-1-yl)-N-methyl-o-toluamide

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Procedure

A solution of 29.8 grams (0.2 mole) of N-methyl-o-toluamide in 600 milliliters of dry tetrahydrofuran is treated dropwise with 275 milliliters (0.44 mole) of n-butyl lithium in hexane, while maintaining the temperature at 0° C. to 10° C. After the addition is complete, the mixture is stirred at 0° C. to 10° C. for 2 hours. The cooling bath is removed and a solution of 32.2 grams (0.2 mole) of N-methyl phthalimide in 330 milliliters of tetrahydrofuran is added dropwise. The temperature is maintained at 20° - 25° C. during the addition, afterwhich it is stirred for 11/2 hours at room temperature. The resulting mixture is cooled in ice and quenched by the addition of saturated ammonium chloride. The layers are separated and the organic layer is washed with ammonium chloride solution, dried over magnesium sulfate, filtered and evaporated in vacuo. The resulting oil is crystallized from ethyl acetate to give α-(1-hydroxy-2-methyl-3-oxoisoindolin-1-yl)-N-methyl-o-toluamide, m.p. 175.5 - 177.5.

Workup

  1. temperaturewhile maintaining the temperature at 0° C. to 10° C
  2. additionAfter the addition
  3. customThe cooling bath is removed
  4. temperatureThe temperature is maintained at 20° - 25° C. during the addition, afterwhich it
  5. stirringis stirred for 11/2 hours at room temperature
  6. temperatureThe resulting mixture is cooled in ice
  7. customquenched by the addition of saturated ammonium chloride
  8. customThe layers are separated
  9. washthe organic layer is washed with ammonium chloride solution
  10. dry with materialdried over magnesium sulfate
  11. filtrationfiltered
  12. customevaporated in vacuo
  13. customThe resulting oil is crystallized from ethyl acetate

Sources & evidence

ORD record
ord-5177e300cc5e490b8f07ecde88cbc2aa
Source dataset
uspto-grants-1978_08
Patent number
US04107311

Reaction notes

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