Reaktion #169590

Reaktionsgleichung

azide

toluene

4-tert-butyl 1-methyl 2-(4-chlorophenyl)succinate

TFA

diphenylphosphoryl azide

triethylamine

→

methyl 3-(tert-butoxycarbonylamino)-2-(4-chlorophenyl)propanoate

Ausbeute 79.0%

Lösungsmittel

tert-butanol

DCM

Reaktionsbedingungen

Aufarbeitung

1. 1
   Einengenafter which the reaction mixture was concentrated
2. 2
   Sonstigedried in vacuo overnight
3. 3
   Sonstigeto afford a white solid
4. 4
   Temperaturto warm to room temperature
5. 5
   workup.STIRRINGstirred for four hours to completion
6. 6
   SonstigeThe solution was quenched with 1% citric acid solution
7. 7
   Extraktionextracted with EtOAc (3×)
8. 8
   WaschenThe combined organics were washed with brine
9. 9
   Trocknendried over Na2SO4
10. 10
    Filtrationfiltered
11. 11
    Einengenconcentrated in vacuo
12. 12
    Sonstigeto give a light brown oil
13. 13
    Temperaturcarefully heated to 90° C. with evolution of nitrogen
14. 14
    workup.STIRRINGThe mixture was stirred at 90° C. for 2.5 hours
15. 15
    Temperaturcooled to room temperature
16. 16
    SonstigeThe solution was quenched with saturated NaHCO3 solution
17. 17
    Einengenconcentrated
18. 18
    ExtraktionThe oily mixture was extracted with EtOAc (3×)
19. 19
    Waschenthe combined organics were washed with brine
20. 20
    Trocknendried over MgSO4
21. 21
    Filtrationfiltered
22. 22
    Einengenconcentrated in vacuo
23. 23
    SonstigeThe residue was purified by on silica gel (4:1 hexanes:EtOAc)

Vorschrift

A solution of 4-tert-butyl 1-methyl 2-(4-chlorophenyl)succinate (14.3 g, 47.7 mmol) in DCM (75 mL) was treated with neat TFA (75 mL) at room temperature. The mixture was stirred for five hours to completion, after which the reaction mixture was concentrated and dried in vacuo overnight to afford a white solid. The solid was suspended in toluene (160 mL), cooled to 0° C., and treated successively with diphenylphosphoryl azide (11.2 mL, 52.1 mmol) and triethylamine (13.2 mL, 94.7 mmol). The reaction mixture (homogeneous) was allowed to warm to room temperature and stirred for four hours to completion. The solution was quenched with 1% citric acid solution and extracted with EtOAc (3×). The combined organics were washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo to give a light brown oil. The crude azide was dissolved in tert-butanol (160 mL), treated with neat SnCl4 (1.0M solution, 2.37 mL, 2.37 mmol), and carefully heated to 90° C. with evolution of nitrogen. The mixture was stirred at 90° C. for 2.5 hours and cooled to room temperature. The solution was quenched with saturated NaHCO3 solution and then concentrated. The oily mixture was extracted with EtOAc (3×), and the combined organics were washed with brine, dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by on silica gel (4:1 hexanes:EtOAc) to afford the methyl 3-(tert-butoxycarbonylamino)-2-(4-chlorophenyl)propanoate as a pale yellow oil (11.7 g, 79%). 1H NMR (CDCl3, 400 MHz) δ 7.31 (d, J=8.0 Hz, 2H), 7.20 (d, J=8.0 Hz, 2H), 4.86 (br s, 1H), 3.88 (m, 1H), 3.69 (s, 3H), 3.58 (m, 1H), 3.49 (m, 1H), 1.42 (s, 9H).

Quelle