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

HRID 388699Notes

Reaction equation

HRID 388699 reaction equation
[H-].[Na+].[CH3:3][O:4][C:5]1[CH:6]=[CH:7][C:8]([CH2:11][OH:12])=[CH:9][CH:10]=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.[NH4+].[Cl-]>CN(C=O)C.C(OCC)(=O)C.O>[CH3:3][O:4][C:5]1[CH:10]=[CH:9][C:8]([CH2:11][O:12][C:37]2[C:36]3[C:31](=[C:32]([Cl:42])[C:33]([O:40][CH3:41])=[CH:34][CH:35]=3)[N:30]=[C:29]([Cl:28])[CH:38]=2)=[CH:7][CH:6]=1

Participants

9

Reactant 5

HCID 77384-Methoxybenzyl alcoholHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 3633615-Crown-5HCID 27945162,4,8-Trichloro-7-methoxyquinoline

Product 1

HCID 566051532,8-Dichloro-7-methoxy-4-(4-methoxy-benzyloxy)-quinolineYield 56%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

Sodium hydride (2.74 g, 1.2 eq.) was added portionwise to a solution of p-methoxybenzyl alcohol (8.55 mL, 1.2 eq.) and 15-crown-5 (13.6 mL, 1.2 eq.) in 35 mL of DMF. The mixture was allowed to stir at room temperature for 30 min, and then added to a solution of 2,4,8-trichloro-7-methoxyquinoline (15 g, 1 eq.) in DMF (75 mL) via canula. After 18 hrs of stirring at room temperature, the mixture was poured on 500 mL of water and NH4Cl aqueous. Ethyl acetate (200 mL) was added and the precipitate was filtered. The filtrate was purified by chromatography on silica gel to yield compound 274 in 56% yield. 1H NMR (CDCl3, 400 MHz) δ (ppm) 3.85 (s, 3H), 4.05 (s, 3H), 5.19 (s, 2H), 6.77 (s, 1H), 6.97 (d, J=8.64 Hz, 2H), 7.23 (d, J=9.25 Hz, 1H), 7.41 (d, J=8.64 Hz, 2H), 8.08 (d, J=9.25 Hz, 1H); MS (ESI, EI+): m/z=386.1 (MNa+).

Workup

  1. stirringAfter 18 hrs of stirring at room temperature
  2. filtrationthe precipitate was filtered
  3. customThe filtrate was purified by chromatography on silica gel

Sources & evidence

ORD record
ord-0ab69a72fc144467b9250129d83f8e5c
Source dataset
uspto-grants-2013_02
Patent number
US08377962B2

Reaction notes

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