2,4-Dimethylaniline → Tert-butyl 3-(4-{[(2-(2,4-dimethylphenyl)amino-2-oxoethyl)(2-furylmethyl)amino]methyl}phenyl)-2,2-dimethylpropionate

HRID 353171Notes

Reaction equation

HRID 353171 reaction equation
ON1C2C=CC=CC=2N=N1.CN1CCOCC1.[C:18]([O:22][C:23](=[O:46])[C:24]([CH3:45])([CH3:44])[CH2:25][C:26]1[CH:43]=[CH:42][C:29]([CH2:30][N:31]([CH2:36][C:37]2[O:38][CH:39]=[CH:40][CH:41]=2)[CH2:32][C:33](O)=[O:34])=[CH:28][CH:27]=1)([CH3:21])([CH3:20])[CH3:19].[CH3:47][C:48]1[CH:54]=[C:53]([CH3:55])[CH:52]=[CH:51][C:49]=1[NH2:50]>CN(C)C1C=CN=CC=1.CN(C)C=O.O>[CH3:47][C:48]1[CH:54]=[C:53]([CH3:55])[CH:52]=[CH:51][C:49]=1[NH:50][C:33](=[O:34])[CH2:32][N:31]([CH2:30][C:29]1[CH:42]=[CH:43][C:26]([CH2:25][C:24]([CH3:44])([CH3:45])[C:23]([O:22][C:18]([CH3:19])([CH3:21])[CH3:20])=[O:46])=[CH:27][CH:28]=1)[CH2:36][C:37]1[O:38][CH:39]=[CH:40][CH:41]=1

Participants

8

Reactant 4

HCID 72502,4-DimethylanilineHCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 22708180N-[4-(3-tert-butoxy-2,2-dimethyl-3-oxopropyl)benzyl]-N-(2-furylmethyl)glycine

Product 1

HCID 22708241Tert-butyl 3-(4-{[(2-(2,4-dimethylphenyl)amino-2-oxoethyl)(2-furylmethyl)amino]methyl}phenyl)-2,2-dimethylpropionateYield 91%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

At 0° C., 88 mg (0.648 mmol) of 1-hydroxy-1H-benzotriazole, 124 mg (0.648 mmol) of 1-ethyl-3-(3-dimethylamino)propylcarbodiimide hydrochloride, 151 mg (1.494 mmol) of N-methylmorpholine and 3 mg (0.025 mmol) of 4-dimethylaminopyridine are added to a solution of 200 mg (0.498 mmol) of N-[4-(3-tert-butoxy-2,2-dimethyl-3-oxopropyl)benzyl]-N-(2-furylmethyl)glycine (Example I-12) and 91 mg (0.747 mmol) of 2,4-dimethylaniline in 8 ml of dimethylformamide, and the solution is stirred at this temperature for 1 h. The mixture is then stirred at room temperature for 9 h and then admixed with 10 ml of water. The aqueous phase is extracted 2× with ethyl acetate and the combined organic phases are washed with 1 N hydrochloric acid, sat. NaHCO3 solution and sat. NaCl solution, dried over sodium sulphate and freed from the solvent under reduced pressure. Chromatographic purification of the residue on silica gel (cyclohexane/ethyl acetate 10:1→3:1) gives 228 mg (91%) of tert-butyl 3-(4-{[(2-(2,4-dimethylphenyl)amino-2-oxoethyl)(2-furylmethyl)amino]methyl}phenyl)-2,2-dimethylpropionate.

Workup

  1. customAt 0° C.
  2. stirringThe mixture is then stirred at room temperature for 9 h
  3. extractionThe aqueous phase is extracted 2× with ethyl acetate
  4. washthe combined organic phases are washed with 1 N hydrochloric acid, sat. NaHCO3 solution and sat. NaCl solution
  5. dry with materialdried over sodium sulphate
  6. customChromatographic purification of the residue on silica gel (cyclohexane/ethyl acetate 10:1→3:1)

Sources & evidence

ORD record
ord-abdaf97dea8a47ea874b080cc37bebc8
Source dataset
uspto-grants-2004_06
Patent number
US06750236B2

Reaction notes

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