Reaction #3019

Reaction equation

2,6-dimethoxy-4-methylaniline hydrochloride

N-Boc-glycine

BOP

dimethylformamide

→

N-tert-butyloxycarbonyl-[(2,6-dimethoxy-4-methylphenyl)carbamoyl]methylamine

Yield 96.0%

Solvents

ethyl acetate

triethylamine

diisopropyl ether

Conditions

Workup

1. 1
   workup.WAITThe reaction mixture is left at room temperature for 15 hours
2. 2
   Washthe organic phase is successively washed with 3×200 ml of water, with a 1N aqueous sodium hydroxide solution
3. 3
   DryingThe organic phase is dried over anhydrous sodium sulphate
4. 4
   OtherEvaporation of the solvent
5. 5
   Otherleaves a semi-crystalline residue which

Procedure

6.6 g of N-Boc-glycine and 15.6 g of BOP are successively added to 100 ml of dimethylformamide and then, at 0° C., 14 ml of triethylamine are added dropwise. The mixture is left for 20 minutes at 0° C. and 6.7 g of 2,6-dimethoxy-4-methylaniline hydrochloride are then added portionwise. The reaction mixture is left at room temperature for 15 hours. 400 ml of ethyl acetate are added to the reaction mixture and the organic phase is successively washed with 3×200 ml of water, with a 1N aqueous sodium hydroxide solution and then with water. The organic phase is dried over anhydrous sodium sulphate. Evaporation of the solvent leaves a semi-crystalline residue which is solidified in diisopropyl ether to provide N-tert-butyloxycarbonyl-[(2,6-dimethoxy-4-methylphenyl)carbamoyl]methylamine, in the form of white crystals; M.p.=146° C.; Yield: 96%.

Source