4-Chlorophenyl Isocyanate → HCID 59894917, compound

HRID 2184732Notes

Reaction equation

HRID 2184732 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O.C1C2C(CO[C:47]([NH:49][C@H:50]([C:67]([O:69][CH3:70])=[O:68])[CH2:51][S:52][CH2:53][CH:54]([C:59](=[O:66])[C:60]3[CH:61]=[N:62][CH:63]=[CH:64][CH:65]=3)[CH2:55][C:56]([OH:58])=[O:57])=[O:48])C3C(=CC=CC=3)C=2C=CC=1.[Cl:71][C:72]1[CH:77]=[CH:76][C:75]([N:78]=C=O)=[CH:74][CH:73]=1>C1COCC1.ClCCl>[Cl:71][C:72]1[CH:77]=[CH:76][C:75]([NH:78][C:47]([NH:49][C@H:50]([C:67]([O:69][CH3:70])=[O:68])[CH2:51][S:52][CH2:53][CH:54]([C:59](=[O:66])[C:60]2[CH:61]=[N:62][CH:63]=[CH:64][CH:65]=2)[CH2:55][C:56]([OH:58])=[O:57])=[O:48])=[CH:74][CH:73]=1

Participants

7

Reactant 4

HCID 76934-Chlorophenyl IsocyanateHCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 70109626HCID 70109626, compound

Product 1

HCID 59894917HCID 59894917, compoundYield 12%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

Wang resin (100-200 mesh, 0.66 mmol/g, 70 mg) was treated with triphenylphosphine (34.5 mg), diethyl azodicarboxylate (20.8 μL) and 3-({(2R)-2-[(fluoren-9-ylmethoxy)carbonylamino]-2-(methoxycarbonyl)ethylthio}methyl)-4-oxo-4-(3-pyridyl)butanoic acid (72.3 mg) in THF (0.5 mL) at room temperature for 3 days. The resin was filtered, washed with dimethyl formamide, isopropanol, dichloromethane and ether and dried. The resin was treated with 20% piperidine-dichloromethane (1 mL) solution for 1 h. The resin was filtered, and washed with dimethyl formamide, isopropanol, dichloromethane and ether and dried. The resin was treated with 10 eq of 4-chlorophenyl isocyanate in dichloromethane (6 mL) for two days. The resin was washed with washed with dimethyl formamide, isopropanol, dichloromethane and ether and dried. The resin was treated with 20% trifluoroacetic acid in dichloromethane (5 mL). The solution was filtered, concentrated and purified on HPLC (C-18 prep column, 10% to 90% acetonitrile in water both containing 0.1% TFA) to give 12% of the title compound; ESMS, (M+1)+480.

Workup

  1. filtrationThe resin was filtered
  2. washwashed with dimethyl formamide, isopropanol, dichloromethane and ether
  3. customdried
  4. additionThe resin was treated with 20% piperidine-dichloromethane (1 mL) solution for 1 h
  5. filtrationThe resin was filtered
  6. washwashed with dimethyl formamide, isopropanol, dichloromethane and ether
  7. customdried
  8. washThe resin was washed
  9. washwith washed with dimethyl formamide, isopropanol, dichloromethane and ether
  10. customdried
  11. additionThe resin was treated with 20% trifluoroacetic acid in dichloromethane (5 mL)
  12. filtrationThe solution was filtered
  13. concentrationconcentrated
  14. custompurified on HPLC (C-18 prep column, 10% to 90% acetonitrile in water both containing 0.1% TFA)

Sources & evidence

ORD record
ord-3302f233223043b3bc114abd564ed614
Source dataset
uspto-grants-2002_06
Patent number
US06399606B1

Reaction notes

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