2-Methoxyethanol → Tert-butyl 2-(3-(2-methoxyethoxy)quinolin-6-yl)acetate

HRID 40351

Reaction equation

HRID 40351 reaction equation
[OH:1][C:2]1[CH:3]=[N:4][C:5]2[C:10]([CH:11]=1)=[CH:9][C:8]([CH2:12][C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])=[CH:7][CH:6]=2.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH3:39][O:40][CH2:41][CH2:42]O.N(C(OC(C)(C)C)=O)=NC(OC(C)(C)C)=O>CCOC(C)=O.C1C=CC=CC=1>[CH3:39][O:40][CH2:41][CH2:42][O:1][C:2]1[CH:3]=[N:4][C:5]2[C:10]([CH:11]=1)=[CH:9][C:8]([CH2:12][C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])=[CH:7][CH:6]=2

Participants

7

Reactant 4

HCID 80192-MethoxyethanolHCID 11776TriphenylphosphineHCID 97268Di-tert-butyl azodicarboxylateHCID 57691372Tert-butyl 2-(3-hydroxyquinolin-6-yl)acetate

Product 1

HCID 57690925Tert-butyl 2-(3-(2-methoxyethoxy)quinolin-6-yl)acetateYield 82%

Reagents, catalysts & solvents 2

HCID 241BenzeneSolventHCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
0 °C

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.

Workup

  1. customthen sealed with a septum
  2. temperatureto warm to rt
  3. temperaturemaintained 20 h
  4. customThe solution was then partitioned between saturated aqueous
  5. customNH4Cl, and the layers separated
  6. extractionThe aqueous layer was extracted with EtOAc (2×50 mL)
  7. washthe combined organic layers were washed with brine
  8. dry with materialdried (MgSO4)
  9. concentrationconcentrated in vacuo
  10. customThe resulting residue was purified by MPLC (Teledine Isco combiFlash Companion), 80 g SiO2, solvent system

Sources & evidence

ORD record
ord-8dfdfb4c74224e3191f4dafaaac5c262
Source dataset
uspto-grants-2013_09
Patent number
US08524900B2

Linked notes

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