Triphenylphosphine → HCID 178512850, compound

HRID 433034Notes

Reaction equation

HRID 433034 reaction equation
[NH2:1][C@H:2]([C:24]([OH:26])=O)[CH2:3][CH2:4][CH2:5][NH:6][C:7](=[NH:23])[N:8](C(OC(C)(C)C)=O)C(OC(C)(C)C)=O.[OH:27][C:28]1[CH:29]=[C:30]([CH:34]=[C:35]([OH:38])[C:36]=1[Br:37])[C:31]([OH:33])=O.CC(C)[N:41]=C=NC(C)C.C1C=CC2N(O)N=NC=2C=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Cl:77][C:78]1[CH:83]=[C:82]([Cl:84])[CH:81]=[CH:80][C:79]=1[CH2:85][CH2:86]O.CC(OC(/N=N/C(OC(C)C)=O)=O)C>CN(C=O)C.C1COCC1>[Br:37][C:36]1[C:35]([OH:38])=[CH:34][C:30]([C:31]([NH:1][C@H:2]([C:24](=[O:26])[NH2:41])[CH2:3][CH2:4][CH2:5][NH:6][C:7]([NH2:8])=[NH:23])=[O:33])=[CH:29][C:28]=1[O:27][CH2:86][CH2:85][C:79]1[CH:80]=[CH:81][C:82]([Cl:84])=[CH:83][C:78]=1[Cl:77]

Participants

10

Reactant 7

HCID 11776TriphenylphosphineHCID 12734DiisopropylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 860234-Bromo-3,5-dihydroxybenzoic acidHCID 27340992,4-Dichlorophenethyl alcoholHCID 5363146Diisopropyl azodicarboxylateHCID 178454311HCID 178454311, compound

Product 1

HCID 178512850HCID 178512850, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

Rink resin (500 mg; loading 0.3 mmol/g) functionalized with Arg(Boc)2 was coupled with 176 mg of 3,5-dihydroxy-4-bromobenzoic acid in the presence of DIC (110 mg) and HOBt (78 mg) in DMF. The resin was then washed and treated with a 30% solution of benzyltrimethylammonium hydroxide in DMF for 1 h. The resin was washed with DMF, 10% acetic acid in DMF, DMF, and DCM and dried in vacuo for 3 h. The dried resin was washed with anhydrous THF and mixed with 0.2 mmol of triphenylphosphane and 0.2 mmol of 2-(2,4-dichlorophenyl)ethanol in 2 ml of dry THF. The suspension of the resin was cooled in a refrigerator for 16 min and 50 μl (0.2 mmol) of DIAD in 0.5 ml of dry THF were added. Coupling was continued overnight at room temperature. The resin was washed with dry THF and the coupling was repeated for additional 8 h. The resin was washed and dried, and the final product was cleaved off and processed as described in Example 1.

Workup

  1. washThe resin was then washed
  2. additiontreated with a 30% solution of benzyltrimethylammonium hydroxide in DMF for 1 h
  3. washThe resin was washed with DMF, 10% acetic acid in DMF, DMF, and DCM
  4. customdried in vacuo for 3 h
  5. washThe dried resin was washed with anhydrous THF
  6. additionThe suspension of the resin
  7. temperaturewas cooled in a refrigerator for 16 min
  8. washThe resin was washed with dry THF
  9. waitthe coupling was repeated for additional 8 h
  10. washThe resin was washed
  11. customdried

Sources & evidence

ORD record
ord-6b819f116e134274b935d0f22d796e7d
Source dataset
uspto-grants-2003_12
Patent number
US06664393B2

Reaction notes

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