تفاعل #169590

معادلة التفاعل

azide

toluene

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

TFA

diphenylphosphoryl azide

triethylamine

→

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

المردود 79.0%

المذيبات

tert-butanol

DCM

ظروف التفاعل

المعالجة

1. 1
   تركيزafter which the reaction mixture was concentrated
2. 2
   أخرىdried in vacuo overnight
3. 3
   أخرىto afford a white solid
4. 4
   درجة الحرارةto warm to room temperature
5. 5
   workup.STIRRINGstirred for four hours to completion
6. 6
   أخرىThe solution was quenched with 1% citric acid solution
7. 7
   استخلاصextracted with EtOAc (3×)
8. 8
   غسيلThe combined organics were washed with brine
9. 9
   تجفيفdried over Na2SO4
10. 10
    ترشيحfiltered
11. 11
    تركيزconcentrated in vacuo
12. 12
    أخرىto give a light brown oil
13. 13
    درجة الحرارةcarefully heated to 90° C. with evolution of nitrogen
14. 14
    workup.STIRRINGThe mixture was stirred at 90° C. for 2.5 hours
15. 15
    درجة الحرارةcooled to room temperature
16. 16
    أخرىThe solution was quenched with saturated NaHCO3 solution
17. 17
    تركيزconcentrated
18. 18
    استخلاصThe oily mixture was extracted with EtOAc (3×)
19. 19
    غسيلthe combined organics were washed with brine
20. 20
    تجفيفdried over MgSO4
21. 21
    ترشيحfiltered
22. 22
    تركيزconcentrated in vacuo
23. 23
    أخرىThe residue was purified by on silica gel (4:1 hexanes:EtOAc)

الإجراء التجريبي

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).

المصدر