4-Methoxybenzyl alcohol → 2,8-Dichloro-7-methoxy-4-(4-methoxy-benzyloxy)-quinoline

HRID 925950Notes

Reaction equation

HRID 925950 reaction equation
[H-].[Na+].[CH3:3][O:4][C:5]1[CH:12]=[CH:11][C:8]([CH2:9][OH:10])=[CH:7][CH:6]=1.C1OCCOCCOCCOCCOC1.[Cl:28][C:29]1[CH:38]=[C:37](Cl)[C:36]2[C:31](=[C:32]([Cl:42])[C:33]([O:40][CH3:41])=[CH:34][CH:35]=2)[N:30]=1>CN(C=O)C.O>[Cl:28][C:29]1[CH:38]=[C:37]([O:10][CH2:9][C:8]2[CH:11]=[CH:12][C:5]([O:4][CH3:3])=[CH:6][CH:7]=2)[C:36]2[C:31](=[C:32]([Cl:42])[C:33]([O:40][CH3:41])=[CH:34][CH:35]=2)[N:30]=1

Participants

7

Reactant 4

HCID 77384-Methoxybenzyl alcoholHCID 24758Sodium hydrideHCID 3633615-Crown-5HCID 27945162,4,8-Trichloro-7-methoxyquinoline

Product 1

HCID 566051532,8-Dichloro-7-methoxy-4-(4-methoxy-benzyloxy)-quinolineYield 38%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Procedure

NaH (60% in oil) (670 mg, 1.2 eq.) was added portionwise to a stirred solution of p-methoxybenzylalcohol (2.31 g, 1.2 eq.) and 15-crown-5 (3.32 mL, 1.2 eq.) in anhydrous DMF (10 mL). The mixture was stirred at room temperature for 30 min. Compound 220d (3.66 g, 1 eq.) in anhydrous DMF (25 mL) was then added and the reaction mixture was stirred at room temperature for 16 hrs. The reaction mixture was then poured into water (300 mL), extracted with EtOAC, dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude material was purified by chromatography on silica gel (petroleum ether/DCM, 50/50) to give compound 221d as a yellow solid in 38% yield. 1H NMR (CDCl3, 376 MHz) δ (ppm) 3.86 (s, 3H), 4.05 (s, 3H). 5.20 (s, 2H), 6.77 (s, 1H), 6.98 (d, J=8.53 Hz, 2H), 7.23 (d, J=9.41, 1H), 7.42 (d, J=8.53 Hz, 2H), 8.08 (d, J=9.41 Hz, 1H).

Workup

  1. stirringthe reaction mixture was stirred at room temperature for 16 hrs
  2. extractionextracted with EtOAC
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe crude material was purified by chromatography on silica gel (petroleum ether/DCM, 50/50)

Sources & evidence

ORD record
ord-d86554817f764bf2aa1d8d9148322cb6
Source dataset
uspto-grants-2016_03
Patent number
US09284307B2

Reaction notes

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