Sodium Iodide → HCID 10349517, compound

HRID 487229Notes

Reaction equation

HRID 487229 reaction equation
[C:1]1([O:7][P:8]([CH2:17][NH:18][C@@H:19]([CH2:28][C:29]2[CH:34]=[CH:33][C:32]([C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)=[CH:31][CH:30]=2)[C:20]([NH:22][CH2:23][CH2:24][C:25]([OH:27])=[O:26])=[O:21])([O:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(N(CC)CC)C.Cl[CH2:49][C:50]([N:52]([CH2:55][CH3:56])[CH2:53][CH3:54])=[O:51].[I-].[Na+]>C(OCC)(=O)C>[C:1]1([O:7][P:8]([CH2:17][NH:18][C@@H:19]([CH2:28][C:29]2[CH:30]=[CH:31][C:32]([C:35]3[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=3)=[CH:33][CH:34]=2)[C:20]([NH:22][CH2:23][CH2:24][C:25]([O:27][CH2:49][C:50](=[O:51])[N:52]([CH2:55][CH3:56])[CH2:53][CH3:54])=[O:26])=[O:21])([O:10][C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=2)=[O:9])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 8471TriethylamineHCID 16844Chloro-N,N-diethylacetamideHCID 132812Cgs 25462

Product 1

HCID 10349517HCID 10349517, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of (S)-N-[2-(diphenylphosphonomethylamino)-3-(4-biphenylyl)-propionyl]-3-aminopropionic acid (0.6 g, 1.07 mmol) in ethyl acetate (9 mL) is added triethylamine (0.19 mL, 1.34 mmol) followed by 2-chloro-N,N-diethylacetamide (0.18 mL, 1.34 mmol) and sodium iodide (20 mg, 0.13 mmol). The solution is heated under nitrogen at 80° for 12 hours. The precipitate is filtered off and the filtrate is treated with water (10 mL) and 2N HCl (0.5 mL). The organic layer is separated, dried over sodium sulfate and filtered. After evaporation of the solvent under reduced pressure, the semi-solid residue is purified by flash chromatography on silica gel, eluting with ethyl acetate. The title compound is finally crystallized from ethyl acetate-hexane to yield N,N-diethylcarbamoylmethyl (S)-N-[2-(diphenylphosphonomethylamino)-3-(4-biphenylyl)-propionyl]-3-aminopropionate, m.p. 68°-74°, [α]D =-20.55 (c=0.84, CHCl3).

Workup

  1. temperatureThe solution is heated under nitrogen at 80° for 12 hours
  2. filtrationThe precipitate is filtered off
  3. additionthe filtrate is treated with water (10 mL) and 2N HCl (0.5 mL)
  4. customThe organic layer is separated
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. customAfter evaporation of the solvent under reduced pressure
  8. customthe semi-solid residue is purified by flash chromatography on silica gel
  9. washeluting with ethyl acetate
  10. customThe title compound is finally crystallized from ethyl acetate-hexane

Sources & evidence

ORD record
ord-3f7f67c7fa91428a90d053b64c784f7d
Source dataset
uspto-grants-1994_03
Patent number
US05294632

Reaction notes

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