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

HRID 925980Notes

Reaction equation

HRID 925980 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 cannula. 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-e1155c567edc49c89629869babf170fa
Source dataset
uspto-grants-2016_03
Patent number
US09284307B2

Reaction notes

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