Potassium Carbonate → [2-(3-Methoxyphenyl)-8-methylquinolin-3-yl]methanol

HRID 1948734Notes

Reaction equation

HRID 1948734 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.[CH3:15][O:16][C:17]1[CH:18]=[C:19](B(O)O)[CH:20]=[CH:21][CH:22]=1.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.O.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>[CH3:15][O:16][C:17]1[CH:22]=[C:21]([C:2]2[C:11]([CH2:12][OH:13])=[CH:10][C:9]3[C:4](=[C:5]([CH3:14])[CH:6]=[CH:7][CH:8]=3)[N:3]=2)[CH:20]=[CH:19][CH:18]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 865104(2-Chloro-8-methylquinolin-3-yl)methanolHCID 2734370(3-Methoxyphenyl)boronic acid

Product 1

HCID 67197902[2-(3-Methoxyphenyl)-8-methylquinolin-3-yl]methanolYield 76%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
150 °C

Procedure

To a solution of (2-chloro-8-methylquinolin-3-yl)methanol (300 mg, 1.45 mmol) in 1,4-dioxane/water (4 mL/1 mL) was added 3-methoxyphenylboronic acid (261 mg, 1.74 mmol), K2CO3 (400 mg, 2.9 mmol) and Pd(PPh3)4 (167 mg, 0.145 mmol). The mixture was degassed and heated in a microwave at 150° C. for 1 h. The solvent was removed in vacuo and the residue dissolved in DCM (50 mL) and washed with water (2×10 mL). The organic layer was separated, dried (MgSO4), filtered and the solvent removed in vacuo. Purification by column chromatography (SiO2, 10-20% EtOAc in Petrol 40-60) yielded the title compound (306 mg, 76%) as a colourless gum. δH (CDCl3) 8.25 (s, 1H), 7.66 (d, J 8.2 Hz, 1H), 7.54 (d, J 7.1 Hz, 1H), 7.32-7.45 (m, 2H), 7.21-7.26 (m, 2H), 6.96-7.00 (m, 1H), 4.79 (s, 2H), 3.85 (s, 3H), 2.81 (s, 3H), 2.06 (s, 1H). LCMS (ES+) 280 (M+H)+, RT 3.03 minutes (Method 5).

Workup

  1. customThe mixture was degassed
  2. customThe solvent was removed in vacuo
  3. dissolutionthe residue dissolved in DCM (50 mL)
  4. washwashed with water (2×10 mL)
  5. customThe organic layer was separated
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. customthe solvent removed in vacuo
  9. customPurification by column chromatography (SiO2, 10-20% EtOAc in Petrol 40-60)

Sources & evidence

ORD record
ord-9bb04fe8588942faa1c8ec476904fa34
Source dataset
uspto-grants-2013_03
Patent number
US08399483B2

Reaction notes

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