Potassium Carbonate → HCID 86653033, compound

HRID 1948727Notes

Reaction equation

HRID 1948727 reaction equation
Cl[C:2]1[C:11]([CH:12]=[O:13])=[CH:10][C:9]2[C:4](=[C:5]([CH3:14])[CH:6]=[CH:7][CH:8]=2)[N:3]=1.[S:15]1[CH:19]=[CH:18][CH:17]=[C:16]1B(O)O.C([O-])([O-])=O.[K+].[K+].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:14][C:5]1[CH:6]=[CH:7][CH:8]=[C:9]2[C:4]=1[N:3]=[C:2]([C:16]1[S:15][CH:19]=[CH:18][CH:17]=1)[C:11]([CH:12]=[O:13])=[CH:10]2

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 11776TriphenylphosphineHCID 6890822-Chloro-8-methylquinoline-3-carboxaldehydeHCID 27339602-Thiopheneboronic acid

Product 1

HCID 86653033HCID 86653033, compoundYield 75.8%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolvent

Conditions

Temperature
115 °C

Procedure

A mixture of 2-chloro-8-methylquinoline-3-carboxaldehyde (234 mg, 1.14 mmol), 2-thiopheneboronic acid (248 mg, 1.94 mmol), K2CO3 (315 mg, 2.28 mmol), palladium(II) acetate (10 mg, 0.045 mmol) and triphenylphosphine (48 mg, 0.182 mmol) in water (2 mL) was degassed. 1,4-Dioxane (6 mL) was added and the mixture further degassed, then heated at 115° C. for 2 h under microwave irradiation. The reaction mixture was filtered through Celite, washed with DCM and water and the filtrate was concentrated in vacuo. The residue was partitioned between DCM (100 mL) and H2O (50 mL). The aqueous layer was re-extracted with DCM (50 mL) and the combined organic layers were dried (MgSO4) and concentrated in vacuo. Purification by column chromatography (SiO2, DCM) gave 8-methyl-2-(thien-2-yl)quinoline-3-carboxaldehyde (219 mg) as a yellow solid. This was dissolved in MeOH/DCM (6 mL/3 mL) and to it was added sodium borohydride (59 mg, 1.56 mmol). The reaction mixture was stirred at room temperature, quenched by the addition of glacial AcOH (0.1 mL) and the solvent removed in vacuo. The residue was partitioned between DCM (200 mL) and 5% aqueous Na2CO3 solution (40 mL). The aqueous layer was re-extracted with DCM (60 mL) and the combined organic layers were dried (MgSO4) and concentrated in vacuo. Purification by column chromatography (SiO2, 3% EtOAc in DCM) gave the title compound as a yellow solid (110 mg, 38%). δH (CDCl3) 8.27 (s, 1H), 7.70 (d, J 6 Hz, 1H), 7.65 (d, J 12 Hz, 1H), 7.55 (d, J 12 Hz, 1H), 7.48 (d, J 9 Hz, 1H), 7.36-7.45 (m, 1H), 7.15-7.20 (m, 1H), 5.10 (d, J 5.8 Hz, 2H), 2.85 (s, 3H), 1.94 (t, J 12 Hz, 1H). LCMS (ES+) 256.2 (M+H)+, RT 4.06 minutes (Method 4).

Workup

  1. customwas degassed
  2. addition1,4-Dioxane (6 mL) was added
  3. filtrationThe reaction mixture was filtered through Celite
  4. washwashed with DCM and water
  5. concentrationthe filtrate was concentrated in vacuo
  6. customThe residue was partitioned between DCM (100 mL) and H2O (50 mL)
  7. extractionThe aqueous layer was re-extracted with DCM (50 mL)
  8. dry with materialthe combined organic layers were dried (MgSO4)
  9. concentrationconcentrated in vacuo
  10. customPurification by column chromatography (SiO2, DCM)

Sources & evidence

ORD record
ord-56ff5147978847d3933a5015c540bbf9
Source dataset
uspto-grants-2013_03
Patent number
US08399483B2

Reaction notes

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