Potassium Carbonate → (8-Methyl-2-phenylquinolin-3-yl)methanol

HRID 1948721Notes

Reaction equation

HRID 1948721 reaction equation
Cl[C:2]1[C:11]([CH2:12][OH:13])=[CH:10][C:9]2[C:4](=[C:5]([CH3:14])[CH:6]=[CH:7][CH:8]=2)[N:3]=1.C([O-])([O-])=O.[K+].[K+].[C:21]1(B(O)O)[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>COCCOC.O.CC([O-])=O.CC([O-])=O.[Pd+2].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:14][C:5]1[CH:6]=[CH:7][CH:8]=[C:9]2[C:4]=1[N:3]=[C:2]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[C:11]([CH2:12][OH:13])=[CH:10]2

Participants

8

Reactant 3

HCID 11430Potassium CarbonateHCID 66827Phenylboronic AcidHCID 865104(2-Chloro-8-methylquinolin-3-yl)methanol

Product 1

HCID 57707842(8-Methyl-2-phenylquinolin-3-yl)methanolYield 49%

Reagents, catalysts & solvents 4

HCID 11776TriphenylphosphineCatalystHCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

A mixture of (2-chloro-8-methylquinolin-3-yl)methanol (413 mg, 2.0 mmol) and K2CO3 (828 mg, 6.0 mmol) in DME (7.5 mL) and water (7.5 mL) was degassed (×3). Phenylboronic acid (293 mg, 2.4 mmol), PPh3 (21 mg, 0.08 mmol) and Pd(OAc)2 (4.5 mg, 0.02 mmol) were added, the mixture was degassed, then heated at reflux for 75 minutes. The reaction mixture was allowed to cool to r.t. then extracted with EtOAc (2×20 mL). The combined organic phases were washed with water (20 mL), dried (MgSO4) and evaporated in vacuo. The residue was purified by column chromatography (SiO2, 10-100% EtOAc in heptane) then by preparative HPLC (Method 1). The product obtained was partitioned between EtOAc and 10% aqueous K2CO3 solution. The organic phase was dried (MgSO4) and evaporated in vacuo to give the title compound (241 mg, 49%) as a white solid. δH (CDCl3) 8.31 (s, 1H), 7.68-7.76 (m, 3H), 7.41-7.59 (m, 5H), 4.86 (d, J 5.1 Hz, 2H), 2.82 (s, 3H), 1.85 (t, J 5.5 Hz, 1H). LCMS (ES+) 250.1 (M+H)+, RT 3.52 minutes (Method 3).

Workup

  1. customwas degassed (×3)
  2. customthe mixture was degassed
  3. temperatureheated
  4. temperatureat reflux for 75 minutes
  5. extractionthen extracted with EtOAc (2×20 mL)
  6. washThe combined organic phases were washed with water (20 mL)
  7. dry with materialdried (MgSO4)
  8. customevaporated in vacuo
  9. customThe residue was purified by column chromatography (SiO2, 10-100% EtOAc in heptane)
  10. customThe product obtained
  11. customwas partitioned between EtOAc and 10% aqueous K2CO3 solution
  12. dry with materialThe organic phase was dried (MgSO4)
  13. customevaporated in vacuo

Sources & evidence

ORD record
ord-306c7c72a28b4ca49de64686b8dbcd96
Source dataset
uspto-grants-2013_03
Patent number
US08399483B2

Reaction notes

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