Trimethylphosphine → HCID 58460146, compound

HRID 1946503Notes

Reaction equation

HRID 1946503 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][N:9]2[C:13]3[CH:14](O)[CH2:15][CH2:16][C:12]=3[N:11]=[C:10]2[C:18]([CH3:21])([CH3:20])[CH3:19])=[CH:4][CH:3]=1.[CH2:22]([O:24][C:25]([CH:27]([C:33]([O:35][CH2:36][CH3:37])=[O:34])[C:28]([O:30][CH2:31][CH3:32])=[O:29])=[O:26])[CH3:23].CP(C)C.N(C(OC(C)C)=O)=NC(OC(C)C)=O>C1(C)C=CC=CC=1.CC1CCCO1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:8][N:9]2[C:13]3[CH:14]([C:27]([C:33]([O:35][CH2:36][CH3:37])=[O:34])([C:25]([O:24][CH2:22][CH3:23])=[O:26])[C:28]([O:30][CH2:31][CH3:32])=[O:29])[CH2:15][CH2:16][C:12]=3[N:11]=[C:10]2[C:18]([CH3:21])([CH3:20])[CH3:19])=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 68983TrimethylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 80471Triethyl methanetricarboxylateHCID 58460153HCID 58460153, compound

Product 1

HCID 58460146HCID 58460146, compound

Reagents, catalysts & solvents 2

HCID 1140TolueneSolvent2×HCID 73012-MethyltetrahydrofuranSolvent

Procedure

To a suspension of Intermediate 34 (300 mg) and triethylmethanetricarboxylate (0.417 ml) in toluene (3.5 ml) and methyltetrahydrofuran (3.50 ml), stirred at RT under an inert atmosphere of nitrogen, was added trimethylphosphine, 1M in toluene (1.97 ml). The resulting solution was cooled to −78° C. and diisopropyl azodicarboxylate (0.39 ml) was added dropwise via syringe and the reaction was stirred at −78° C. for 45 mins. The reaction mixture was removed from the cold bath and allowed to warm to RT and stirred under N2 atmosphere overnight. Reaction mixture concentrated in vacuo. The residue was taken up in DCM (20 ml) and washed with water (20 mL). The 2 phases were separated, the organic extract was dried (hydrophobic frit) and concentrated under vacuum. The residue was purified on silica using a cyclohexane:ethyl acetate 0-100% gradient. The desired fractions were combined and concentrated under vacuum to give the title compound (496 mg). LC/MS MH+ 519, Rt 3.53 min (5 minute run)

Workup

  1. temperatureThe resulting solution was cooled to −78° C.
  2. stirringthe reaction was stirred at −78° C. for 45 mins
  3. customThe reaction mixture was removed from the cold bath
  4. temperatureto warm to RT
  5. stirringstirred under N2 atmosphere overnight
  6. customReaction mixture
  7. concentrationconcentrated in vacuo
  8. washwashed with water (20 mL)
  9. customThe 2 phases were separated
  10. extractionthe organic extract
  11. customwas dried (hydrophobic frit)
  12. concentrationconcentrated under vacuum
  13. customThe residue was purified on silica using a cyclohexane
  14. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-9ec85dee4c6342a6a1eb3c1bb497f8ac
Source dataset
uspto-grants-2013_03
Patent number
US08399444B2

Reaction notes

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