Potassium Phosphate, Tribasic → (2-(Biphenyl-2-yl)-8-methylquinolin-3-yl)methanol

HRID 1948726Notes

Reaction equation

HRID 1948726 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:15]1([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[C:16](B(O)O)=[CH:17][CH:18]=[CH:19][CH:20]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>COCCOC.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>[C:15]1([C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=2)[CH:16]=[CH:17][CH:18]=[CH:19][C:20]=1[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

Participants

7

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 865104(2-Chloro-8-methylquinolin-3-yl)methanolHCID 4589187Biphenyl-2-boronic acid

Product 1

HCID 57707898(2-(Biphenyl-2-yl)-8-methylquinolin-3-yl)methanolYield 27%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of (2-chloro-8-methylquinolin-3-yl)methanol (342 mg, 1.65 mmol), 2-biphenylboronic acid (392 mg, 1.98 mmol) and K3PO4 (399 mg, 1.88 mmol) in DME (4 mL) and water (1 mL) was degassed. Pd(PPh3)4 (95 mg, 0.08 mmol) was added, the mixture was degassed and heated in the microwave at 120° C. for 1 h. The reaction mixture was allowed to cool and extracted with EtOAc (150 mL). The organic layer was washed with water (50 mL), separated, dried (MgSO4) and concentrated in vacuo. Purification by column chromatography (SiO2, 0-100% EtOAc in heptane) gave the title compound (145 mg, 27%) as a white crystalline solid. δH (MeOD-d4) 8.19 (s, 1H), 7.71 (d, J 8.1 Hz, 1H), 7.40-7.66 (m, 6H), 7.15-7.20 (m, 2H), 7.08-7.12 (m, 3H), 4.30-4.40 (br m, 1H), 4.11-4.22 (br m, 1H), 2.70 (s, 3H). LCMS (ES+) 326.3 (M+H)+, RT 3.98 minutes (Method 3).

Workup

  1. customwas degassed
  2. customthe mixture was degassed
  3. temperatureto cool
  4. extractionextracted with EtOAc (150 mL)
  5. washThe organic layer was washed with water (50 mL)
  6. customseparated
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated in vacuo
  9. customPurification by column chromatography (SiO2, 0-100% EtOAc in heptane)

Sources & evidence

ORD record
ord-8bf6f35ad9da4c878129bb16a39d043b
Source dataset
uspto-grants-2013_03
Patent number
US08399483B2

Reaction notes

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