Reacción #169590

Ecuación de reacción

azide

toluene

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

TFA

diphenylphosphoryl azide

triethylamine

→

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

Rendimiento 79.0%

Disolventes

tert-butanol

DCM

Condiciones de reacción

Tratamiento posterior

1. 1
   Concentraciónafter which the reaction mixture was concentrated
2. 2
   Otrodried in vacuo overnight
3. 3
   Otroto afford a white solid
4. 4
   Temperaturato warm to room temperature
5. 5
   workup.STIRRINGstirred for four hours to completion
6. 6
   OtroThe solution was quenched with 1% citric acid solution
7. 7
   Extracciónextracted with EtOAc (3×)
8. 8
   LavadoThe combined organics were washed with brine
9. 9
   Secadodried over Na2SO4
10. 10
    Filtraciónfiltered
11. 11
    Concentraciónconcentrated in vacuo
12. 12
    Otroto give a light brown oil
13. 13
    Temperaturacarefully heated to 90° C. with evolution of nitrogen
14. 14
    workup.STIRRINGThe mixture was stirred at 90° C. for 2.5 hours
15. 15
    Temperaturacooled to room temperature
16. 16
    OtroThe solution was quenched with saturated NaHCO3 solution
17. 17
    Concentraciónconcentrated
18. 18
    ExtracciónThe oily mixture was extracted with EtOAc (3×)
19. 19
    Lavadothe combined organics were washed with brine
20. 20
    Secadodried over MgSO4
21. 21
    Filtraciónfiltered
22. 22
    Concentraciónconcentrated in vacuo
23. 23
    OtroThe residue was purified by on silica gel (4:1 hexanes:EtOAc)

Procedimiento

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).

Fuente