N-Methylaniline → Methyl 4-{[methyl(phenyl)amino]methyl}benzoate

HRID 970824Notes

Reaction equation

HRID 970824 reaction equation
C(OC1C=CC(CO)=CC=1)CC1C=CC=CC=1.[CH3:18][O:19][C:20](=[O:29])[C:21]1[CH:26]=[CH:25][C:24]([CH:27]=O)=[CH:23][CH:22]=1.[CH3:30][NH:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[CH3:18][O:19][C:20](=[O:29])[C:21]1[CH:26]=[CH:25][C:24]([CH2:27][N:31]([CH3:30])[C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)=[CH:23][CH:22]=1

Participants

6

Reactant 4

HCID 7515N-MethylanilineHCID 15294Methyl 4-FormylbenzoateHCID 5049666Sodium triacetoxyborohydrideHCID 12990905(4-Phenethyloxyphenyl)methanol

Product 1

HCID 28829589Methyl 4-{[methyl(phenyl)amino]methyl}benzoate

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

Following the procedure in J.Org. Chem. 1996, 61 (11), 3849-3862, methyl-4-formylbenzoate (0.821 g, 5.00 mmol) was dissolved in 1,2-dichloroethane (75 ml) at room temperature. N-methylaniline (0.542 ml, 5.00 mmol) was added followed by sodium triacetoxyborohydride (1.484 g, 7.00 mmol). The mixture was allowed to stir at room temperature overnight. The mixture was quenched with saturated sodium bicarbonate solution and extracted with diethyl ether. The organic extracts were dried over anhydrous sodium sulfate and concentrated en vacuo. The residue was purified by-flash chromatography on silica eluted with 4:1 hexane/acetone to give 1.097 g (85.9%) of a slightly yellow oil of 4-[(methyl-phenyl-amino)-methyl]-benzoic acid methyl ester. Reduction to {4-[(methyl-phenyl-amino)-methyl]-phenyl}-methanol, condensation with(R)-2-isocyanato-3-phenyl-propionate of formula 5 and hydrolysis as described for example in Example 1 Steps 2-4, yielded about 1.5 g of 2-{4-[(methyl-phenyl-amino)-methyl]-benzyloxycarbonylamino}-3-phenyl-propionic 169, mp. 69.6-70.1° C.

Workup

  1. customThe mixture was quenched with saturated sodium bicarbonate solution
  2. extractionextracted with diethyl ether
  3. dry with materialThe organic extracts were dried over anhydrous sodium sulfate
  4. concentrationconcentrated en vacuo
  5. customThe residue was purified by-flash chromatography on silica
  6. washeluted with 4:1 hexane/acetone

Sources & evidence

ORD record
ord-4d55d71cf2584a3abd65aa4b3cbb9ff5
Source dataset
uspto-grants-2007_12
Patent number
US07312230B2

Reaction notes

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