Reaktion #517096

Reaktionsgleichung

tert-butyl N-((benzyloxy)carbonyl)4-O-((benzyloxy)carbonyl)-3-iodo-L-tyrosinate

toluene

cyclopentene

tri-ortho-tolylphosphine

→

tert-butyl 3-cyclopentyl-L-tyrosinate

Ausbeute 93.0%

Lösungsmittel

EtOAc

MeOH

hexane

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe solution was deoxygenated
2. 2
   Sonstigeby bubbling nitrogen through for 10 min
3. 3
   workup.ADDITIONwas treated with 0.182 g of Pd(OAc)2 and 1.24 nL of Et3N
4. 4
   SonstigeThe bomb was flushed with nitrogen
5. 5
   Sonstigesealed
6. 6
   TemperaturThe vessel was cooled to RT
7. 7
   Sonstigepurged with nitrogen
8. 8
   FiltrationThe reaction mixture was filtered
9. 9
   Sonstigeto remove solids
10. 10
    Einengenthe filtrate was concentrated in vacuo to dryness
11. 11
    workup.DISSOLUTIONThe residue was dissolved in 200 mL of EtOAc
12. 12
    Waschenthe solution was washed with water (4×100 mL)
13. 13
    Trocknendried over anhydrous NaSO4
14. 14
    Einengenconcentrated
15. 15
    Sonstigeto give a thick brown oil
16. 16
    SonstigeIn addition, 0.90 g (25%) of the Rf=0.40 material was obtained
17. 17
    Sonstigeresulting from loss of the O-benzyloxycarbonyl group
18. 18
    SonstigeThe crude product was purified by flash chromatography (SiO2, EtOAc)

Vorschrift

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 nL 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 componenets 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-benzyloxycarbonyl group. The bis(benzyloxycarbonyl) olefin mixture (2.00 g) was 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.

Quelle