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

HRID 369814Notes

Reaction equation

HRID 369814 reaction equation
C(OC([NH:11][C@H:12]([C:24]([O:26][CH2:27][CH3:28])=[O:25])[CH2:13][C:14]1[CH:19]=[CH:18][C:17]([N+:20]([O-])=O)=[CH:16][C:15]=1I)=O)C1C=CC=CC=1.[CH:29]1[CH2:33][CH2:32][CH2:31][CH:30]=1.C1(C)C=CC=CC=1.C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>CC([O-])=O.CC([O-])=O.[Pd+2].CO.CCOC(C)=O.CCCCCC.CCN(CC)CC>[NH2:20][C:17]1[CH:18]=[CH:19][C:14]([CH2:13][C@@H:12]([C:24]([O:26][CH2:27][CH3:28])=[O:25])[NH2:11])=[C:15]([CH:29]2[CH2:33][CH2:32][CH2:31][CH2:30]2)[CH:16]=1

Participants

10

Reactant 4

HCID 1140TolueneHCID 8882CyclopenteneHCID 80271Tri-o-tolylphosphineHCID 54039325ethyl N-((benzyloxy)carbonyl)-2-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 tri-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-4225d44599c94491974eecaadb2ae300
Source dataset
uspto-grants-2000_10
Patent number
US06140100

Reaction notes

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