Reaction #314336

Reaction equation

[(S)-1-(2-amino-4-iodo-phenylcarbamoyl)-2-methyl-propyl]-carbamic acid tert-butyl ester

[(S)-1-(2-amino-5-iodo-phenylcarbamoyl)-2-methyl-propyl]-carbamic acid tert-butyl ester

(S)-2-tert-butoxycarbonylamino-3-methyl-butyric acid

4-iodo-benzene-1,2-diamine

diisopropylethyl amine

O-benzotriazol-1-yl-N,N, N′,N′-tetramethyluronium

sodium carbonate

→

(R)-5-[4-(2-Hydroxy-ethoxy)-phenyl]-3-[(S)-1-(5-iodo-1H-benzoimidazol-2-yl)-2-methyl-propyl]-imidazolidine-2,4-dione

Solvents

N,N-dimethylformamide

N,N-dimethylformamide

Conditions

Workup

1. 1
   Extractionthe reaction mixture was extracted with ethyl acetate
2. 2
   Washthe organic layer was washed with aqueous sodium carbonate solution and brine
3. 3
   Dryingdried over sodium sulfate
4. 4
   Filtrationfiltered
5. 5
   Concentrationconcentrated
6. 6
   Otherto give

Procedure

To the solution of (S)-2-tert-butoxycarbonylamino-3-methyl-butyric acid (0.33 g, 1.5 mmol), 4-iodo-benzene-1,2-diamine (0.35 g, 1.5 mmol) and diisopropylethyl amine (0.8 mL, 4.5 mmol) in N,N-dimethylformamide (6 mL) was added dropwise a solution of O-benzotriazol-1-yl-N,N, N′,N′-tetramethyluronium hexaflurorophosphate (0.71 g, 1.75 mmol) N,N-dimethylformamide (2 mL). The reaction mixture was stirred for 12 hours at room temperature. After adding aqueous sodium carbonate solution, the reaction mixture was extracted with ethyl acetate and the organic layer was washed with aqueous sodium carbonate solution and brine, dried over sodium sulfate, filtered, and concentrated to give a mixture of regioisomers, [(S)-1-(2-amino-4-iodo-phenylcarbamoyl)-2-methyl-propyl]-carbamic acid tert-butyl ester and [(S)-1-(2-amino-5-iodo-phenylcarbamoyl)-2-methyl-propyl]-carbamic acid tert-butyl ester (0.65 g, 100%).

Source