Triphenylphosphine → HCID 178431455, compound

HRID 993482Notes

Reaction equation

HRID 993482 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[CH3:37])[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.C[Si](C([Si](C)(C)C)C(N)=O)(C)C.[Cl:89][C:90]1[CH:95]=[C:94]([Cl:96])[CH:93]=[CH:92][C:91]=1[CH2:97][CH2:98]O.CC(OC(/N=N/C(OC(C)C)=O)=O)C>CN(C=O)C.C1COCC1>[C:24]([C@@H:2]([NH:1][C:31](=[O:33])[C:30]1[CH:34]=[C:35]([OH:38])[C:36]([CH3:37])=[C:28]([O:27][CH2:98][CH2:97][C:91]2[CH:92]=[CH:93][C:94]([Cl:96])=[CH:95][C:90]=2[Cl:89])[CH:29]=1)[CH2:3][CH2:4][CH2:5][NH:6][C:7]([NH2:8])=[NH:23])(=[O:26])[NH2:41]

Participants

11

Reactant 8

HCID 11776TriphenylphosphineHCID 12734DiisopropylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 27340992,4-Dichlorophenethyl alcoholHCID 27480453,5-Dihydroxy-4-methylbenzoic AcidHCID 5363146Diisopropyl azodicarboxylateHCID 11708267BistrimethylsilylacetamidHCID 178454311HCID 178454311, compound

Product 1

HCID 178431455HCID 178431455, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

Rink resin (239 mg; loading 0.43 mmol/g) functionalized with Arg(Boc)2 was coupled with 106 mg of 3,5-dihydroxy-4-methylbenzoic acid in the presence of DIC (85 mg) and HOBt (90 mg) in DMF (1.5 ml). The resin was then washed and treated with a 15% solution of benzyltrimethylammonium hydroxide in DMF for 45 min. The resin was washed with DMF, 10% acetic acid in DMF, DMF and DCM and dried in vacuo for 4 h. The dried resin was washed with anhydrous THF and mixed with 145 mg (0.5 mmole) of triphenylphosphane and 25 μl of bistrimethylsilylacetamide in THF and kept at room temperature for 1 h. In a separate vial a mixture of 100 mg (0.2 mmol) of 2-(2,4-dichlorophenyl)ethanol and 100 μl of DIAD in dry THF was prepared. The reaction mixture was added to the resin which had previously been cooled in a refrigerator for 10 min. Coupling was continued at room temperature overnight. 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 15% solution of benzyltrimethylammonium hydroxide in DMF for 45 min
  3. washThe resin was washed with DMF, 10% acetic acid in DMF, DMF and DCM
  4. customdried in vacuo for 4 h
  5. washThe dried resin was washed with anhydrous THF
  6. customwas prepared
  7. additionThe reaction mixture was added to the resin which
  8. temperaturehad previously been cooled in a refrigerator for 10 min
  9. waitCoupling was continued at room temperature overnight
  10. washThe resin was washed
  11. customdried

Sources & evidence

ORD record
ord-07d2bdb2d09140029947298213553af4
Source dataset
uspto-grants-2002_10
Patent number
US06472562B1

Reaction notes

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