Trifluoroacetic acid → (S)-5-(Biphenyl-4-yl)-4-[(dimethylphosphonomethyl)-amino]-2-pentenoic acid ethyl ester

HRID 1655291Notes

Reaction equation

HRID 1655291 reaction equation
[CH2:1]([O:3][C:4](=[O:29])[CH:5]=[CH:6][C@@H:7]([NH:21]C(OC(C)(C)C)=O)[CH2:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[CH:11][CH:10]=1)[CH3:2].FC(F)(F)C(O)=O.C(=O)(O)[O-].[Na+].C(N(CC)C(C)C)(C)C.FC(S(O[CH2:59][P:60]([O:64][CH3:65])([O:62][CH3:63])=[O:61])(=O)=O)(F)F>C(Cl)Cl.O>[CH2:1]([O:3][C:4](=[O:29])[CH:5]=[CH:6][C@@H:7]([NH:21][CH2:59][P:60]([O:64][CH3:65])([O:62][CH3:63])=[O:61])[CH2:8][C:9]1[CH:10]=[CH:11][C:12]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[CH:13][CH:14]=1)[CH3:2]

Participants

8

Reactant 5

HCID 6422Trifluoroacetic acidHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 22098913Dimethylphosphonomethyl trifluoromethylsulfonateHCID 54107369(S)-4-t-Butoxycarbonylamino-5-(biphenyl-4-yl)-pentenoic acid ethyl ester

Product 1

HCID 53707898(S)-5-(Biphenyl-4-yl)-4-[(dimethylphosphonomethyl)-amino]-2-pentenoic acid ethyl ester

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent4×

Procedure

(S)-4-t-Butoxycarbonylamino-5-(biphenyl-4-yl)-pentenoic acid ethyl ester (1.2 g, 3.03 mmol) is stirred for 1 hour in a 1/l mixture of trifluoroacetic acid and methylene chloride (10 mL). A saturated aqueous solution of sodium bicarbonate (10 mL) is added and the product is extracted in methylene chloride (20 mL). The organic layer is dried over anhydrous sodium sulfate, filtered and cooled to 0° under nitrogen. To that solution is added N,N-diisopropylethylamine (0.633 mL, 3.63 mmol) in methylene chloride (2 mL), followed by a solution of dimethylphosphonomethyl trifluoromethylsulfonate (Tetrahedron Lett., 1986, 1477; 907 mg, 3.33 mmol) in methylene chloride (2 mL). The mixture is stirred at room temperature for 18 hours. Water (20 mL) and methylene chloride (20 mL) are added. The organic layer is separated, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue is purified by flash-chromatography on silica gel, eluting with ethyl acetate to afford (S)-5-(biphenyl-4-yl)-4-[(dimethylphosphonomethyl)-amino]-2-pentenoic acid ethyl ester as a pale yellow oil (Rf=0.3 in EtOAc).

Workup

  1. extractionthe product is extracted in methylene chloride (20 mL)
  2. dry with materialThe organic layer is dried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. temperaturecooled to 0° under nitrogen
  5. customThe organic layer is separated
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue is purified by flash-chromatography on silica gel
  10. washeluting with ethyl acetate

Sources & evidence

ORD record
ord-31649ef94bf645108d735536107941de
Source dataset
uspto-grants-1993_10
Patent number
US05250522

Reaction notes

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