Water → (2,6-Dimethoxy-4-methylphenyl)(2-methylaminophenyl) Ketone

HRID 862402

Reaction equation

HRID 862402 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH3:11])[CH:6]=[C:7]([O:9][CH3:10])[CH:8]=1.C([Li])CCC.[CH3:17][N:18]1C(=O)O[C:21](=[O:22])[C:20]2=[CH:26][CH:27]=[CH:28][CH:29]=[C:19]12.O>O1CCCC1.CCCCCC.C(OCC)(=O)C>[CH3:10][O:9][C:7]1[CH:6]=[C:5]([CH3:11])[CH:4]=[C:3]([O:2][CH3:1])[C:8]=1[C:21]([C:20]1[CH:26]=[CH:27][CH:28]=[CH:29][C:19]=1[NH:18][CH3:17])=[O:22]

Participants

8

Reactant 4

HCID 962WaterHCID 25160N-Methylisatoic anhydrideHCID 778443,5-DimethoxytolueneHCID 178418339Butyllithium

Product 1

HCID 57322216(2,6-Dimethoxy-4-methylphenyl)(2-methylaminophenyl) KetoneYield 78%

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolventHCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-20 °C

Procedure

To a solution of 30 g of 3,5-dimethoxytoluene in 400 ml of tetrahydrofuran are added, at a temperature in the region of -20° C., 129 ml of 1.6M butyllithium in hexane. Once the introduction is complete, the reaction mixture is brought to a temperature of 0° C. and is then stirred for 1 hour. It is cooled to -20° C. and 36.67 g of N-methylisatoic anhydride are added portionwise. The mixture is allowed to return to room temperature and is stirred over 2 hours, followed by addition of 500 ml of water and extraction with ethyl acetate. The organic phase is washed with water, dried over sodium sulphate and evaporated under vacuum. The residue is purified by chromatography on silica gel, eluent: toluene/ethyl acetate 9/1. The fractions of pure product are concentrated under vacuum and the residue is crystallized from isopropyl ether, filtered and dried. Beige crystals melting at 215° C. are obtained; Yield=78%.

Workup

  1. customis brought to a temperature of 0° C.
  2. customto return to room temperature
  3. stirringis stirred over 2 hours
  4. washThe organic phase is washed with water
  5. dry with materialdried over sodium sulphate
  6. customevaporated under vacuum
  7. customThe residue is purified by chromatography on silica gel, eluent
  8. concentrationThe fractions of pure product are concentrated under vacuum
  9. customthe residue is crystallized from isopropyl ether
  10. filtrationfiltered
  11. customdried

Sources & evidence

ORD record
ord-47e41d771d9c4d0280e185636e9a06cc
Source dataset
uspto-grants-1998_02
Patent number
US05719143

Linked notes

Loading…