Benzyl Alcohol → 3-Benzyloxy-6-methoxy-[1,5]naphthyridine-4-carbonitrile

HRID 633790Notes

Reaction equation

[H-].[Na+].Cl[C:4]1[CH:5]=[N:6][C:7]2[C:12]([C:13]=1[C:14]#[N:15])=[N:11][C:10]([O:16][CH3:17])=[CH:9][CH:8]=2.[CH2:18]([OH:25])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.C(OCC)(=O)C>O1CCCC1>[CH2:18]([O:25][C:4]1[CH:5]=[N:6][C:7]2[C:12]([C:13]=1[C:14]#[N:15])=[N:11][C:10]([O:16][CH3:17])=[CH:9][CH:8]=2)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1

Participants

Conditions

Temperature: -30 °C

Procedure

Sodium hydride (70 mg, 1.73 mmol, 2.0 eq) is added at −30° C. to a stirred solution of 3-chloro-6-methoxy-[1,5]naphthyridine-4-carbonitrile (190 mg, 0.87 mmol, 1.0 eq) and benzyl alcohol (187 mg, 1.73 mmol, 2.0 eq) in tetrahydrofuran (12 mL). After 2 hours stirring at −30° C., the reaction mixture is concentrated and extracted with ethyl acetate (3×20 mL) and water (20 mL). The combined organic layers are dried over sodium sulfate, filtered and concentrated to give a residue that is purified by column chromatography (silica gel, eluent: petroleum ether:ethyl acetate, 5:1, v/v) to afford 3-benzyloxy-6-methoxy-[1,5]naphthyridine-4-carbonitrile as a light yellow solid (160 mg, 64% yield).

Workup

concentrationthe reaction mixture is concentrated
extractionextracted with ethyl acetate (3×20 mL) and water (20 mL)
dry with materialThe combined organic layers are dried over sodium sulfate
filtrationfiltered
concentrationconcentrated
customto give a residue that
customis purified by column chromatography (silica gel, eluent

Sources & evidence

ORD record: ord-aa221c11e9504fd6904aaa45a4b466d4
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09321788B2

Reaction notes

Loading…