Acetic Acid → Fmoc-4-Amino-L-phenylalanine

HRID 393433Notes

Reaction equation

HRID 393433 reaction equation
[CH:1]1[C:13]2[CH:12]([CH2:14][O:15][C:16]([NH:18][C@H:19]([C:34]([OH:36])=[O:35])[CH2:20][C:21]3[CH:26]=[CH:25][C:24]([NH:27]C(OCC=C)=O)=[CH:23][CH:22]=3)=[O:17])[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1.C(O)(=O)C.C([SnH](CCCC)CCCC)CCC>ClCCl.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[NH2:27][C:24]1[CH:23]=[CH:22][C:21]([CH2:20][C@@H:19]([C:34]([OH:36])=[O:35])[NH:18][C:16]([O:15][CH2:14][CH:12]2[C:11]3[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=3[C:5]3[C:13]2=[CH:1][CH:2]=[CH:3][CH:4]=3)=[O:17])=[CH:26][CH:25]=1

Participants

6

Reactant 3

HCID 176Acetic Acid2×HCID 5948Tributylstannane4×HCID 538288754-(Allyloxycarbonylamino)-N-Fmoc-L-phenylalanine

Product 1

HCID 7019927Fmoc-4-Amino-L-phenylalanine

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalyst2×HCID 6344DichloromethaneSolvent2×

Procedure

A 500 mL cylindrical glass vessel equipped with a coarse glass frit was charged with N-[(9H-fluoren-9-ylmethoxy)carbonyl]-4-[[(2-propenyloxy)carbonyl]amino]-L-phenylalanine substituted Wang resin (10 g, 7.5 mmol) obtained from Example 61 and a solution prepared from bis(triphenylphosphine)palladium dichloride (1.6 g, 2.3 mmol) and acetic acid (5 mL, 83 mmol) in dried dichloromethane (150 mL). The resulting mixture was agitated for 30 minutes followed by the addition of tri-n-butyl tin hydride (20 mL, 74.3 mmol). The resulting mixture was agitated for 1 hr. To the mixture was added tri-n-butyl tin hydride (10 mL, 37 mmol). Agitation was continued for 1 hour and the mixture was filtered. To the resulting resin was added a solution prepared from bis(triphenylphosphine)palladium dichloride (1.6 g, 2.3 mmol) and acetic acid (5 mL, 83 mmol) in dry dichloromethane (150 mL). The mixture was agitated for 30 minutes followed by the addition of tri-n-butyl tin hydride (20 mL, 74.3 mmol). The resulting mixture was agitated 1 hour. To the mixture was added additional tri-n-butyl tin hydride (10 mL, 37.15 mmol). Agitation was continued for 1 hour. After the second deprotection cycle, the mixture was washed with dichloromethane (2×100 mL), methanol (2×100 mL) and dimethylformamide (2×100 mL) to give 4-amino-N-[(9H-fluoren-9-ylmethoxy)carbonyl]-L-phenylalanine on Wang resin suitable for use in subsequent steps.

Workup

  1. customA 500 mL cylindrical glass vessel equipped with a coarse glass frit
  2. stirringThe resulting mixture was agitated for 1 hr
  3. waitAgitation was continued for 1 hour
  4. filtrationthe mixture was filtered
  5. additionTo the resulting resin was added a solution
  6. stirringThe mixture was agitated for 30 minutes
  7. stirringThe resulting mixture was agitated 1 hour
  8. waitAgitation was continued for 1 hour
  9. washAfter the second deprotection cycle, the mixture was washed with dichloromethane (2×100 mL), methanol (2×100 mL) and dimethylformamide (2×100 mL)

Sources & evidence

ORD record
ord-15cfcc4dc30640f1a5f88ab658d07aaf
Source dataset
uspto-grants-2004_10
Patent number
US06806365B2

Reaction notes

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