Toluene → Ethyl 4-amino-2-cyclopentyl-l-phenylalaninate

HRID 429922Notes

Reaction equation

HRID 429922 reaction equation
I[C:2]1[CH:13]=[C:12]([N+:14]([O-])=O)[CH:11]=[CH:10][C:3]=1[CH2:4][C@@H:5]([C:7]([O-:9])=[O:8])[NH2:6].[CH:17]1[CH2:21][CH2:20][CH2:19][CH:18]=1.[C:22]1(C)C=CC=C[CH:23]=1.C1(C)C=CC=CC=1P>CC([O-])=O.CC([O-])=O.[Pd+2].CO.CCOC(C)=O.CCCCCC.CCN(CC)CC>[NH2:14][C:12]1[CH:11]=[CH:10][C:3]([CH2:4][C@@H:5]([C:7]([O:9][CH2:22][CH3:23])=[O:8])[NH2:6])=[C:2]([CH:17]2[CH2:21][CH2:20][CH2:19][CH2:18]2)[CH:13]=1

Participants

10

Reactant 4

HCID 1140TolueneHCID 8882CyclopenteneHCID 15049146(2-Methylphenyl)phosphaneHCID 1317229992-iodo-4-nitro-L-phenylalaninate

Product 1

HCID 54108695Ethyl 4-amino-2-cyclopentyl-l-phenylalaninate

Reagents, catalysts & solvents 5

HCID 167845palladium(II) acetateCatalystHCID 887MethanolSolventHCID 8058HexaneSolventHCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Procedure

According to example 151, 1.65 g of ethyl N-(benzyloxy)carbonyl)2-iodo-4-nitro-L-phenylalaninate was subjected to Heck coupling with 20 mL of cyclopentene using 60 mL of toluene, 0.074 g of Pd(OAc)2, 0.20 g of ti-ortho-tolylphosphine, and 0.51 mL of Et3N. The reaction was carried out at 110° C. for 24 h. Analysis of the crude product by tlc (SiO2, 8:2 hexane:EtOAc) indicated a major product at Rf=0.40 and minor components at Rf=0.38, 0.60, and 0.95. The Rf=0.40 material was isolated by flash chromatography on silica gel (8:2 hexane:EtOAc). This afforded 1.03 g (71%) of the desired olefin mixture as a clear liquid. This material was subjected to catalytic hydrogenation at 45 psi for 18 h using 55 mL of MeOH and 0.25 g of 10% Pd(C). The crude product was purified by flash chromatography (SiO2, 99:1 EtOAc:MeOH) to give 0.56 g (61% for both steps) of ethyl 4-amino-2-cyclopentyl-L-phenylalaninate as a thick transparent oil.

Workup

  1. customThe Rf=0.40 material was isolated by flash chromatography on silica gel (8:2 hexane:EtOAc)
  2. waitThis material was subjected to catalytic hydrogenation at 45 psi for 18 h
  3. customThe crude product was purified by flash chromatography (SiO2, 99:1 EtOAc:MeOH)

Sources & evidence

ORD record
ord-9e8d306b0c8743188971a6d58557a277
Source dataset
uspto-grants-2001_11
Patent number
US06319702B1

Reaction notes

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