Sodium hydride → 6-(5-Methyl-3-phenyl-isoxazol-4-ylmethoxy)-pyridine-2-carbonitrile

HRID 1897077Notes

Reaction equation

[CH3:1][C:2]1[O:6][N:5]=[C:4]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[C:3]=1[CH2:13][OH:14].Cl[C:16]1[N:21]=[C:20]([C:22]#[N:23])[CH:19]=[CH:18][CH:17]=1.[H-].[Na+].C1OCCOCCOCCOCCOCCOC1>C1(C)C=CC=CC=1.C(OCC)(=O)C>[CH3:1][C:2]1[O:6][N:5]=[C:4]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[C:3]=1[CH2:13][O:14][C:16]1[N:21]=[C:20]([C:22]#[N:23])[CH:19]=[CH:18][CH:17]=1

Participants

Conditions

Temperature: 50 °C

Procedure

To a solution of (5-methyl-3-phenyl-isoxazol-4-yl)-methanol (189 mg, 1.0 mmol) and 6-chloropyridine-2-carbonitrile (150 mg, 1.0 mmol) in toluene (10 mL) was added sodium hydride (55% dispersion in mineral oil, 100 mg, 2.0 mmol) and the mixture heated at 50° C. for 6 h. Then 18-crown-6 (18 mg) was added and the mixture heated at 100° C. overnight. The mixture was then diluted with ethyl acetate and washed with water. The aqueous layers were extracted with ethyl acetate (10 mL) and the combined organic layers were dried over sodium sulfate. Purification by chromatography (SiO2, heptane:ethyl acetate=7:3) afforded the title compound (70 mg, 24%) as a white solid after trituration with diisopropylether. MS: m/e=292.0 [M+H]+.

Workup

temperaturethe mixture heated at 100° C. overnight
washwashed with water
extractionThe aqueous layers were extracted with ethyl acetate (10 mL)
dry with materialthe combined organic layers were dried over sodium sulfate
customPurification by chromatography (SiO2, heptane:ethyl acetate=7:3)

Sources & evidence

ORD record: ord-fd08f88dd8a5439fa09f861e019f7a56
Source dataset: uspto-grants-2013_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08518974B2

Reaction notes

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