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

HRID 29745Notes

Reaction equation

HRID 29745 reaction equation
S(Cl)(Cl)=O.[CH2:5]([O:12][C:13]([NH:15][CH:16]([CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)[C:17]([NH:19][CH:20]([P:24](=[O:27])([OH:26])[OH:25])[CH:21]([CH3:23])[CH3:22])=[O:18])=[O:14])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.[CH3:35][O:36][C:37](=[O:51])[CH:38](O)[CH2:39][CH2:40][CH2:41][NH:42][C:43]([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])=[O:44].C(OCC)(=O)C>CN(C=O)C>[CH3:35][O:36][C:37](=[O:51])[CH:38]([O:27][P:24]([CH:20]([NH:19][C:17](=[O:18])[CH:16]([NH:15][C:13]([O:12][CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)=[O:14])[CH2:28][C:29]1[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=1)[CH:21]([CH3:22])[CH3:23])([OH:26])=[O:25])[CH2:39][CH2:40][CH2:41][NH:42][C:43]([O:45][C:46]([CH3:48])([CH3:47])[CH3:49])=[O:44]

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 24386Thionyl ChlorideHCID 543300255-Tert-butoxycarbonylamino-2-hydroxy-pentanoic acid methyl esterHCID 54345348[1-(2-Benzyloxycarbonylamino-3-phenyl-propionylamino)-2-methyl-propyl]-phosphonic acid

Product 1

HCID 570512352-{[1-(2-Benzyloxycarbonylamino-3-phenyl-propionylamino)-2-methyl-propyl]-hydroxy-phosphinoyloxy}-5-tert-butoxycarbonylamino-pentanoic acid methyl esterYield 66.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
-5 °C

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%).

Workup

  1. stirringthe mixture was stirred for 90 min at room temperature
  2. washthe mixture was washed with 1 M HCl
  3. customdried
  4. concentrationconcentrated under reduced pressure
  5. customThe crude product was purified

Sources & evidence

ORD record
ord-14d06849be6746f8b5ca2cbcf3d08b8f
Source dataset
uspto-grants-2008_09
Patent number
US07423012B2

Reaction notes

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