반응 #517096

반응 방정식

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

toluene

cyclopentene

tri-ortho-tolylphosphine

→

tert-butyl 3-cyclopentyl-L-tyrosinate

수율 93.0%

용매

EtOAc

MeOH

hexane

반응 조건

후처리

1. 1
   기타The solution was deoxygenated
2. 2
   기타by 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
   기타The bomb was flushed with nitrogen
5. 5
   기타sealed
6. 6
   온도The vessel was cooled to RT
7. 7
   기타purged with nitrogen
8. 8
   여과The reaction mixture was filtered
9. 9
   기타to remove solids
10. 10
    농축the filtrate was concentrated in vacuo to dryness
11. 11
    workup.DISSOLUTIONThe residue was dissolved in 200 mL of EtOAc
12. 12
    세척the solution was washed with water (4×100 mL)
13. 13
    건조dried over anhydrous NaSO4
14. 14
    농축concentrated
15. 15
    기타to give a thick brown oil
16. 16
    기타In addition, 0.90 g (25%) of the Rf=0.40 material was obtained
17. 17
    기타resulting from loss of the O-benzyloxycarbonyl group
18. 18
    기타The crude product was purified by flash chromatography (SiO2, EtOAc)

실험 절차

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.

출처