Trifluoroacetic acid → (S)-4-(biphenyl-4-yl)-3-[(dimethylphosphonomethyl)-amino]-butyric acid methyl ester

HRID 1078680Notes

Reaction equation

HRID 1078680 reaction equation
[CH3:1][O:2][C:3](=[O:27])[C@@H:4](N)[CH:5](C(OC(C)(C)C)=O)[CH2:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[CH:9][CH:8]=1.FC(F)(F)C(O)=O.C([N:38]([CH:41](C)C)CC)(C)C.FC(S(OC[P:53]([O:57][CH3:58])([O:55][CH3:56])=[O:54])(=O)=O)(F)F>C(OCC)(=O)C.C(Cl)Cl>[CH3:1][O:2][C:3](=[O:27])[CH2:4][C@@H:5]([NH:38][CH2:41][P:53]([O:57][CH3:58])([O:55][CH3:56])=[O:54])[CH2:6][C:7]1[CH:8]=[CH:9][C:10]([C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=2)=[CH:11][CH:12]=1

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 81531DiisopropylethylamineHCID 22098913Dimethylphosphonomethyl trifluoromethylsulfonateHCID 70084322(S)-3-t-Butoxycarbonyl-amino-4-(biphenyl-4-yl)-butyric acid methyl ester

Product 1

HCID 54030507(S)-4-(biphenyl-4-yl)-3-[(dimethylphosphonomethyl)-amino]-butyric acid methyl ester

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

(S)-3-t-Butoxycarbonyl-amino-4-(biphenyl-4-yl)-butyric acid methyl ester (716 mg, 2 mmol) is stirred for 1 hour in a 1/1 mixture of trifluoroacetic acid and methylene chloride (5 mL). Ethyl acetate (20 mL) is added and the solution is washed with saturated sodium bicarbonate (20 mL). The organic layer is separated, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue is dissolved in methylene chloride (10 mL) and cooled to 0° under nitrogen. Diisopropyl ethylamine (0.42 mL, 2.4 mmol) is added, followed by a solution of dimethylphosphonomethyl trifluoromethylsulfonate (Tetrahedron Lett., 1986, 1477; 545 mg, 2.2 mmol). The mixture is stirred for 18 hours at room temperature. The solution is washed with saturated sodium bicarbonate, water and brine. The organic layer is dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue is purified by flash-chromatography to afford (S)-4-(biphenyl-4-yl)-3-[(dimethylphosphonomethyl)-amino]-butyric acid methyl ester as a white solid, m.p. 67°.

Workup

  1. washthe solution is washed with saturated sodium bicarbonate (20 mL)
  2. customThe organic layer is separated
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. dissolutionThe residue is dissolved in methylene chloride (10 mL)
  7. temperaturecooled to 0° under nitrogen
  8. washThe solution is washed with saturated sodium bicarbonate, water and brine
  9. dry with materialThe organic layer is dried over anhydrous sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customThe residue is purified by flash-chromatography

Sources & evidence

ORD record
ord-7ebd4375877a4ca28cf2b6c0f1f63895
Source dataset
uspto-grants-1996_08
Patent number
US05550119

Reaction notes

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