Cyclohexane → 2-[8-(Benzyloxy)-5-chloroquinolin-7-yl]-1-[3-(5-methyl-2-thienyl)phenyl]ethanol

HRID 551124Notes

Reaction equation

HRID 551124 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:8]2[S:9][C:10]([CH3:13])=[CH:11][CH:12]=2)[CH:5]=[CH:6][CH:7]=1.C([Li])CCC.C1CCCCC1.[CH2:25]([O:32][C:33]1[C:34]([CH2:44][CH:45]=[O:46])=[CH:35][C:36]([Cl:43])=[C:37]2[C:42]=1[N:41]=[CH:40][CH:39]=[CH:38]2)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1>O1CCCC1>[CH2:25]([O:32][C:33]1[C:34]([CH2:44][CH:45]([C:2]2[CH:7]=[CH:6][CH:5]=[C:4]([C:8]3[S:9][C:10]([CH3:13])=[CH:11][CH:12]=3)[CH:3]=2)[OH:46])=[CH:35][C:36]([Cl:43])=[C:37]2[C:42]=1[N:41]=[CH:40][CH:39]=[CH:38]2)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1

Participants

6

Reactant 4

HCID 8078CyclohexaneHCID 598296762-(3-Bromo-phenyl)-5-methyl-thiopheneHCID 59829696[8-(Benzyloxy)-5-chloroquinolin-7-yl]acetaldehydeHCID 178418339Butyllithium

Product 1

HCID 671716842-[8-(Benzyloxy)-5-chloroquinolin-7-yl]-1-[3-(5-methyl-2-thienyl)phenyl]ethanolYield 46%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a stirring solution of 2-(3-bromo-phenyl)-5-methyl-thiophene (0.395 mmol) in tetrahydrofuran (4 mL) at −78° C. was slowly added a 2M solution of n-butyllithium in cyclohexane (0.435 mmol, 1.1 eq.). The resulting solution was stirred 30 min at −78° C. and solid [8-(benzyloxy)-5-chloroquinolin-7-yl]acetaldehyde (0.395 mmol) was added. Stirring at −78° C. was continued for 10 min and the reaction was allowed to warm to room temperature and was stirred 1 h. The reaction mixture was then quenched with saturated aqueous ammonium chloride solution (10 mL) and extracted with ethyl acetate (3×10 mL). The combined organic layers were dried (MgSO4), filtered and concentrated to give a yellow oil that was purified by column chromatography using 20% ethyl acetate/hexanes to give the final product as a light yellow solid (0.18 mmol, 46%). MS (ESI) m/z 486.4.

Workup

  1. stirringStirring at −78° C.
  2. waitwas continued for 10 min
  3. temperatureto warm to room temperature
  4. stirringwas stirred 1 h
  5. customThe reaction mixture was then quenched with saturated aqueous ammonium chloride solution (10 mL)
  6. extractionextracted with ethyl acetate (3×10 mL)
  7. dry with materialThe combined organic layers were dried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customto give a yellow oil that
  11. customwas purified by column chromatography

Sources & evidence

ORD record
ord-110bd44710e3455b8429e56320db0e7b
Source dataset
uspto-grants-2011_05
Patent number
US07947712B2

Reaction notes

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