6-Iodoquinolin-3-ol → Tert-butyl 2-(3-hydroxyquinolin-6-yl)acetate

HRID 40300Notes

Reaction equation

HRID 40300 reaction equation
I[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][C:6]([OH:12])=[CH:5]2.[Cl-].[C:14]([O:18][C:19](=[O:22])[CH2:20][Zn+])([CH3:17])([CH3:16])[CH3:15]>C1COCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[OH:12][C:6]1[CH:7]=[N:8][C:9]2[C:4]([CH:5]=1)=[CH:3][C:2]([CH2:20][C:19]([O:18][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:22])=[CH:11][CH:10]=2

Participants

5

Reactant 2

HCID 598430856-Iodoquinolin-3-olHCID 178451183HCID 178451183, compound

Product 1

HCID 57691372Tert-butyl 2-(3-hydroxyquinolin-6-yl)acetate

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
75 °C

Procedure

A stirred solution of 6-iodoquinolin-3-ol (1.76 g, 6 mmol) in THF (10 mL) was treated with 2-tert-butoxy-2-oxoethylzinc chloride (39 ml, 19 mmol) followed by tetrakis(triphenylphosphine)palladium(0) (0.8 g, 0.6 mmol). After the addition, it was heated to reflux (75° C.) under N2. After 3 h, TLC 89368-3-1 showed no sign of starting material. Reaction was stop. The reaction was cooled to rt. Solvent was removed. The residue was stirred in EtOAc/10% EDTA (50 mL/50 mL) solution mixture. After 1 h, the organic layer was separated. The aqueous layer was extracted with more EtOAc (2×25 mL). The combined organic layers were washed with water, brine, dried over MgSO4, and removed solvent. The crude product was purified using SiO2 chromatography (Teledyne Isco RediSep®, P/N 68-2203-026, 12 g SiO2, hex:acetone=80%:20%, Flow=30 mL/min) to afford the desired product as brownish liquid. MS m/z: 260.3 (M+H). Calc'd. for C15H17NO3—259.2.

Workup

  1. additionAfter the addition, it
  2. temperaturewas heated
  3. customReaction
  4. temperatureThe reaction was cooled to rt
  5. customSolvent was removed
  6. waitAfter 1 h
  7. customthe organic layer was separated
  8. extractionThe aqueous layer was extracted with more EtOAc (2×25 mL)
  9. washThe combined organic layers were washed with water, brine
  10. dry with materialdried over MgSO4
  11. customremoved solvent
  12. customThe crude product was purified

Sources & evidence

ORD record
ord-73f8332e057b4960a4642521c138ba68
Source dataset
uspto-grants-2013_09
Patent number
US08524900B2

Reaction notes

Loading…