Diisopropylethylamine → 2-(3-(t-Butoxycarbonylamino)methylphenyl)-3-((1-(benzyloxycarbonyl)amino-2-methylpropyl)(ethoxy)phosphinoyl)propanoic acid methyl ester

HRID 490943Notes

Reaction equation

HRID 490943 reaction equation
[CH2:1]([O:3][P:4]([CH:6]([NH:10][C:11]([O:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:12])[CH:7]([CH3:9])[CH3:8])[OH:5])[CH3:2].CCN(C(C)C)C(C)C.[CH3:30][O:31][C:32](=[O:50])[C:33]([C:35]1[CH:40]=[CH:39][CH:38]=[C:37]([CH2:41][NH:42][C:43]([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])=[O:44])[CH:36]=1)=[CH2:34]>C(Cl)Cl>[CH3:30][O:31][C:32](=[O:50])[CH:33]([C:35]1[CH:40]=[CH:39][CH:38]=[C:37]([CH2:41][NH:42][C:43]([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])=[O:44])[CH:36]=1)[CH2:34][P:4]([CH:6]([NH:10][C:11]([O:13][CH2:14][C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1)=[O:12])[CH:7]([CH3:9])[CH3:8])([O:3][CH2:1][CH3:2])=[O:5]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 673741311-(Benzyloxycarbonylamino)-2-methylpropylphosphonous acid ethyl esterHCID 673751012-(3-(t-Butoxycarbonylamino)methylphenyl)-propenoic acid methyl ester

Product 1

HCID 673761572-(3-(t-Butoxycarbonylamino)methylphenyl)-3-((1-(benzyloxycarbonyl)amino-2-methylpropyl)(ethoxy)phosphinoyl)propanoic acid methyl esterYield 87.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of 1-(benzyloxycarbonylamino)-2-methylpropyl-phosphonous acid ethyl ester (6.2 g, 20.7 mmol) in 150 ml CH2Cl2 was added DIEA (6.5 mL, 47.5 mmol). The mixture solution was cooled down to 0° C. over an ice-water bath. TMSCI (5.5 mL, 42.0 mmol) was added dropwise under N2. The reaction mixture was stirred at ambient temperature for 2 hours, then cooled to 0° C. again. A solution of 2-(3-(t-butoxycarbonylamino)methylphenyl)-propenoic acid methyl ester (6.7 g, 23.0 mmol) in 15 mL CH2Cl2 was added to the reaction mixture. The resulting reaction mixture was stirred at ambient temperature for 18 hours. The reaction was quenched by 10 mL MeOH, then concentrated in vacuo, and the residue was taken up into 300 mL ethyl acetate. The organic phase was washed with 2 N NaHSO4, water, and brine. The solvent was evaporated in vacuo, and the crude product was purified by flash chromatography on silica gel to afford 2-(3-(t-butoxycarbonylamino)methylphenyl)-3-((1-(benzyloxycarbonyl)amino-2-methylpropyl)(ethoxy)phosphinoyl)propanoic acid methyl ester (10.7 g, 18.1 mmol, 81%) as white solid.

Workup

  1. additionTMSCI (5.5 mL, 42.0 mmol) was added dropwise under N2
  2. temperaturecooled to 0° C. again
  3. customThe resulting reaction mixture
  4. stirringwas stirred at ambient temperature for 18 hours
  5. customThe reaction was quenched by 10 mL MeOH
  6. concentrationconcentrated in vacuo
  7. washThe organic phase was washed with 2 N NaHSO4, water, and brine
  8. customThe solvent was evaporated in vacuo
  9. customthe crude product was purified by flash chromatography on silica gel

Sources & evidence

ORD record
ord-f0a56499d0c04ce4a23af2833244ddda
Source dataset
uspto-grants-2009_05
Patent number
US07528173B2

Reaction notes

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