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

HRID 1976961Notes

Reaction equation

HRID 1976961 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-phenylalanine2×

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 10 g of N-[(9H-fluoren-9-ylmethoxy)carbonyl]-4-[[(2-propenyloxy)carbonyl]amino]-L-phenylalanine substituted Wang resin (10 g) obtained from Example 35 and a solution prepared from Pd(Ph3P)2Cl2 (1.6 g, 2.3 mmol) and acetic acid (5 mL, 83 mmol) in dry 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 hour. 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 Pd(Ph3P)2Cl2 (1.6 g, 2.3 mmol) and acetic acid (5 mL, 83 mmol) in dried 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 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 hour
  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 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-b97eb7a5960448e69f191109c776aafa
Source dataset
uspto-grants-2001_05
Patent number
US06229011B1

Reaction notes

Loading…