Reaction #58023

Reaction equation

Ethyl acetate

Thionyl chloride

[1-(2-benzyloxycarbonylamino-3-phenyl-propionylamino)-2-methyl-propyl]-phosphonic acid

5-tert-Butoxycarbonylamino-2-hydroxy-pentanoic acid methyl ester

→

2-{[1-(2-benzyloxycarbonylamino-3-phenyl-propionylamino)-2-methyl-propyl]-hydroxy-phosphinoyloxy}-5-tert-butoxycarbonylamino-pentanoic acid methyl ester

Yield 66.2%

Solvents

DMF

DMF

Conditions

Workup

1. 1
   workup.STIRRINGthe mixture was stirred for 90 min at room temperature
2. 2
   Washthe mixture was washed with 1 M HCl
3. 3
   Otherdried
4. 4
   Concentrationconcentrated under reduced pressure
5. 5
   OtherThe crude product was purified

Procedure

Thionyl chloride (49 μL, 0.67 mmol) was added dropwise to a solution of [1-(2-benzyloxycarbonylamino-3-phenyl-propionylamino)-2-methyl-propyl]-phosphonic acid (208 mg, 0.48 mmol) in DMF (5 mL) at −20° C. under argon. The mixture was stirred for 35 min at −5° C. A solution of 5-tert-Butoxycarbonylamino-2-hydroxy-pentanoic acid methyl ester (166 mg, 0.67 mmol) in DMF (1 mL) was added and the mixture was stirred for 90 min at room temperature. Ethyl acetate was added and the mixture was washed with 1 M HCl, dried and concentrated under reduced pressure. The crude product was purified using chromathography (CHCl3/MeOH/H2O, 10:1:0→10:5:1) to give 2-{[1-(2-benzyloxycarbonylamino-3-phenyl-propionylamino)-2-methyl-propyl]-hydroxy-phosphinoyloxy}-5-tert-butoxycarbonylamino-pentanoic acid methyl ester (211 mg, 66%).

Source