Reaction #68629

Reaction equation

di-tert-butyl azodicarboxylate

tert-butyl 2-(3-hydroxyquinolin-6-yl)acetate

triphenylphosphine

2-methoxyethanol

→

tert-butyl 2-(3-(2-methoxyethoxy)quinolin-6-yl)acetate

Yield 82.0%

Solvents

—

hexanes

—

hexanes

EtOAc

EtOAc

Benzene

Conditions

Workup

1. 1
   Otherthen sealed with a septum
2. 2
   Temperatureto warm to rt
3. 3
   Temperaturemaintained 20 h
4. 4
   OtherThe solution was then partitioned between saturated aqueous
5. 5
   OtherNH4Cl, and the layers separated
6. 6
   ExtractionThe aqueous layer was extracted with EtOAc (2×50 mL)
7. 7
   Washthe combined organic layers were washed with brine
8. 8
   Dryingdried (MgSO4)
9. 9
   Concentrationconcentrated in vacuo
10. 10
    OtherThe resulting residue was purified by MPLC (Teledine Isco combiFlash Companion), 80 g SiO2, solvent system

Procedure

A flask was charged with tert-butyl 2-(3-hydroxyquinolin-6-yl)acetate (581.04 mg, 2.241 mmol) and triphenylphosphine (1.175 g, 4.482 mmol) then sealed with a septum and an placed under N2. Benzene (10 mL) was added, followed by 2-methoxyethanol (0.8838 ml, 11.20 mmol). The heterogeneous solution was cooled to 0° C., and di-tert-butyl azodicarboxylate (1.032 g, 4.482 mmol) was added as a solid in a single portion. The solution was allowed to warm to rt and maintained 20 h. The solution was then partitioned between saturated aqueous. NH4Cl, and the layers separated. The aqueous layer was extracted with EtOAc (2×50 mL), and the combined organic layers were washed with brine, dried (MgSO4), and concentrated in vacuo. The resulting residue was purified by MPLC (Teledine Isco combiFlash Companion), 80 g SiO2, solvent system: 90:10 hexanes:EtOAc gradient to 50:50 hexanes:EtOAc to give tert-butyl 2-(3-(2-methoxyethoxy)quinolin-6-yl)acetate (585. 2 mg, 82% yield). LRMS (ESI) m/z calcd for C18H24NO4 (M+H) 318.2. found 318.3.

Source