Toluene → HCID 54231770, compound

HRID 369807Notes

Reaction equation

HRID 369807 reaction equation
C(OC([NH:11][C@H:12]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:13][C:14]1[CH:19]=[CH:18][C:17]([O:20]C(OCC2C=CC=CC=2)=O)=[C:16](I)[CH:15]=1)=O)C1C=CC=CC=1.[C:39]1([CH3:45])[CH:44]=[CH:43][CH:42]=CC=1.C1CCCC=1.C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>CO.CCOC(C)=O.CCCCCC>[CH:42]1([C:16]2[CH:15]=[C:14]([CH:19]=[CH:18][C:17]=2[OH:20])[CH2:13][C@@H:12]([C:32]([O:34][C:35]([CH3:36])([CH3:37])[CH3:38])=[O:33])[NH2:11])[CH2:43][CH2:44][CH2:39][CH2:45]1

Participants

8

Reactant 4

HCID 1140TolueneHCID 8882CyclopenteneHCID 80271Tri-o-tolylphosphineHCID 20637705HCID 20637705, compound

Product 1

HCID 54231770HCID 54231770, compoundYield 93%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
110 °C

Procedure

A 300 mL Parr bomb was charged with 5.13 g of tert-butyl N-((benzyloxy)carbonyl)-4-O-((benzyloxy)carbonyl)-3-iodo-L-tyrosinate, 120 mL of toluene, 30 mL of cyclopentene and 0.49 g of tri-ortho-tolylphosphine. The solution was deoxygenated by bubbling nitrogen through for 10 min and was treated with 0.182 g of Pd(OAc)2 and 1.24 mL of Et3N. The bomb was flushed with nitrogen, sealed, and heated to 110° C. for 48 h. The vessel was cooled to RT, purged with nitrogen and opened. The reaction mixture was filtered to remove solids and the filtrate was concentrated in vacuo to dryness. The residue was dissolved in 200 mL of EtOAc and the solution was washed with water(4×100 mL), dried over anhydrous NaSO4 and concentrated to give a thick brown oil. Analysis by tlc (SiO2, 8:2 hexane:EtOAc) indicated two major components at Rf =0.50 and 0.40. The crude mixture was subjected to flash chromatography on silica gel (8:2 hexane:EtOAc). This afforded 2.0 g (43%) of the Rf =0.50 material identified as the bis(benzyloxycarbonyl) olefin mixture by 1H-NMR. In addition, 0.90 g (25%) of the Rf =0.40 material was obtained and was identified as the N-benzyloxycarbonyl olefin mixture resulting from loss of the O-benzyloxycarbonly group. The bis(benzyloxycarbonyl) olefin mixture (2.00 g) ws subjected to catalytic hydrogenation (45 psi) in the presence of 0.35 g of 10% Pd(C) in 70 mL of MeOH for 18 h. The crude product was purified by flash chromatography (SiO2, EtOAc) to give 0.99 g (93%) of tert-butyl 3-cyclopentyl-L-tyrosinate as a transparent glass. The N-Benzyloxycarbonyl olefin mixture (0.90 g) was similarly hydrogenated and purified to afford 0.52 g (83%) of tert-butyl 3-cyclopentyl-L-tyrosinate.

Workup

  1. customThe solution was deoxygenated
  2. customby bubbling nitrogen through for 10 min
  3. additionwas treated with 0.182 g of Pd(OAc)2 and 1.24 mL of Et3N
  4. customThe bomb was flushed with nitrogen
  5. customsealed
  6. temperatureThe vessel was cooled to RT
  7. custompurged with nitrogen
  8. filtrationThe reaction mixture was filtered
  9. customto remove solids
  10. concentrationthe filtrate was concentrated in vacuo to dryness
  11. dissolutionThe residue was dissolved in 200 mL of EtOAc
  12. washthe solution was washed with water(4×100 mL)
  13. dry with materialdried over anhydrous NaSO4
  14. concentrationconcentrated
  15. customto give a thick brown oil
  16. customIn addition, 0.90 g (25%) of the Rf =0.40 material was obtained
  17. customresulting from loss of the O-benzyloxycarbonly group
  18. customThe crude product was purified by flash chromatography (SiO2, EtOAc)

Sources & evidence

ORD record
ord-c1de855d78b24fa09bcb4a291ea4668c
Source dataset
uspto-grants-2000_10
Patent number
US06140100

Reaction notes

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