Diisopropylethylamine → 2-(3-(t-Butoxycarbonylamino)phenyl)-3-((4-phenylbutyl)(hydroxy)-phosphinoyl)propanoic acid methyl ester

HRID 490938Notes

Reaction equation

HRID 490938 reaction equation
[C:1]1([CH2:7][CH2:8][CH2:9][CH2:10][PH:11](=[O:13])[OH:12])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CCN(C(C)C)C(C)C.[CH3:23][O:24][C:25](=[O:42])[C:26]([C:28]1[CH:33]=[CH:32][CH:31]=[C:30]([NH:34][C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH:29]=1)=[CH2:27]>C(Cl)Cl>[CH3:23][O:24][C:25](=[O:42])[CH:26]([C:28]1[CH:33]=[CH:32][CH:31]=[C:30]([NH:34][C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH:29]=1)[CH2:27][P:11]([CH2:10][CH2:9][CH2:8][CH2:7][C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1)([OH:12])=[O:13]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 67376329Methyl 2-(3-(tert-butoxycarbonylamino)phenyl)acrylateHCID 178527055HCID 178527055, compound

Product 1

HCID 673751372-(3-(t-Butoxycarbonylamino)phenyl)-3-((4-phenylbutyl)(hydroxy)-phosphinoyl)propanoic acid methyl esterYield 98.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To 4-phenylbutylphosphinic acid (357 mg, 1.8 mmol) in methylene chloride at 0° C. was added DIEA (0.66 mL, 3.8 mmol), followed by TMSCI (0.47 mL, 3.8 mmol). After 1 hour, 2-(3-(t-butoxycarbonylamino)phenyl)propenoic acid methyl ester (0.5 g, 1.8 mmol) was added and the reaction mixture was allowed to warm to ambient temperature. After 5 hours, the reaction was partitioned between methylene chloride and saturated NaHCO3 solution. The organic layer was washed with 0.1 N sulfuric acid and concentrated in vacuo. The residue was dissolved in 10 mL 3:1 THF:methanol for 18 hours. The reaction was concentrated to provide 2-(3-(t-butoxycarbonylamino)phenyl)-3-((4-phenylbutyl)(hydroxy)phosphinoyl)propanoic acid methyl ester (845 mg) as a white foam.

Workup

  1. waitAfter 5 hours
  2. customthe reaction was partitioned between methylene chloride and saturated NaHCO3 solution
  3. washThe organic layer was washed with 0.1 N sulfuric acid
  4. concentrationconcentrated in vacuo
  5. dissolutionThe residue was dissolved in 10 mL 3:1 THF
  6. waitmethanol for 18 hours
  7. concentrationThe reaction was concentrated

Sources & evidence

ORD record
ord-1caf0a1d00e249c2b2f7cdc4fec8516e
Source dataset
uspto-grants-2009_05
Patent number
US07528173B2

Reaction notes

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