Methyl iodide → Ethyl 2-methoxy-6-methyl-4-[3-(quinolin-2-ylmethoxy)-benzyloxy]-benzoate

HRID 892189Notes

Reaction equation

[OH:1][C:2]1[CH:12]=[C:11]([O:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([O:21][CH2:22][C:23]3[CH:32]=[CH:31][C:30]4[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=4)[N:24]=3)[CH:16]=2)[CH:10]=[C:9]([CH3:33])[C:3]=1[C:4]([O:6][CH2:7][CH3:8])=[O:5].[H-].[Na+].I[CH3:37]>CN(C=O)C>[CH3:37][O:1][C:2]1[CH:12]=[C:11]([O:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([O:21][CH2:22][C:23]3[CH:32]=[CH:31][C:30]4[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=4)[N:24]=3)[CH:16]=2)[CH:10]=[C:9]([CH3:33])[C:3]=1[C:4]([O:6][CH2:7][CH3:8])=[O:5]

Participants

Conditions

Temperature: 50 °C

Procedure

To a solution of ethyl 2-hydroxy-6-methyl-4-[3-(quinolin-2-ylmethoxy)-benzyloxy]-benzoate (150 mg, 0.34 mmol, example 65) in DMF (5 mL) is added sodium hydride (60%, 14 mg, 0.34 mmol) and the reaction is stirred 20 min. Iodomethane (0.03 mL, 0.5 mmol) is added and the reaction is heated at 50° C. for 7 h. The reaction is concentrated in vacuo and the residue is partioned between dichloromethane and aqueous ammonium chloride. The water layer is back-extracted with dichloromethane, the organic phases are combined, dried over magnesium sulfate, filtered and concentrated to yield crude product. The residue is purified by column chromatography (silica, 10 to 20% ethyl acetate in hexanes to provide the title compound; MS (ESI) 458 (M+H)+.

Workup

concentrationThe reaction is concentrated in vacuo
extractionThe water layer is back-extracted with dichloromethane
dry with materialdried over magnesium sulfate
filtrationfiltered
concentrationconcentrated
customto yield crude product
customThe residue is purified by column chromatography (silica, 10 to 20% ethyl acetate in hexanes

Sources & evidence

ORD record: ord-9249f797e23c49c3acdbf5c5471a2da0
Source dataset: uspto-grants-2006_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07005440B1

Reaction notes

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