Phthalic Anhydride → 5-Cyanomethyl-6-ethyl-pyridin-3-yl-acetic acid methyl ester

HRID 900978Notes

Reaction equation

[CH3:1][O:2][C:3](=[O:16])[CH2:4][C:5]1[CH:6]=[N:7][C:8]([CH2:14][CH3:15])=[C:9]([CH2:11][CH:12]=O)[CH:10]=1.Cl.NO.C([N:22](CC)CC)C.C1(=O)OC(=O)C2=CC=CC=C12>C(#N)C.O>[CH3:1][O:2][C:3](=[O:16])[CH2:4][C:5]1[CH:6]=[N:7][C:8]([CH2:14][CH3:15])=[C:9]([CH2:11][C:12]#[N:22])[CH:10]=1

Participants

Conditions

Temperature: 90 °C

Procedure

A solution of 6-ethyl-5-(2-oxo-ethyl)-pyridin-3-yl-acetic acid methyl ester (0.77 g, 3.46 mmol), hydroxylamine hydrochloride (0.26 g, 3.80 mmol) and triethylamine (0.53 mL, 3.80 mmol) in acetonitrile (9 mL, 0.4 M) is stirred under nitrogen at room temperature for 2 h. Phthalic anhydride (0.55 g, 3.71 mmol) is added and the mixture is warmed to 90° C. for 16 h. After cooling to room temperature, water (50 mL) is added and the mixture is extracted with ethyl acetate (50 mL). The organic layer is washed with saturated NaHCO3 (50 mL) and dried over Na2SO4. The product is purified by flash chromatography (20-50% ethyl acetate in n-heptane) to provide 5-cyanomethyl-6-ethyl-pyridin-3-yl-acetic acid methyl ester as a clear oil (0.60 g, 80%): Rf 0.31 (50% ethyl acetate in n-heptane), 1H NMR (CDCl3, 300 MHz) δ 8.44 (s, 1 H), 7.67 (s, 1 H), 3.74 (s, 2 H), 3.73 (s, 3 H), 3.65 (s, 2 H), 2.83 (q, J=7.5 Hz, 2 H), 1.33 (t, J=7.5 Hz, 3 H). ESI-LCMS m/z calcd for C12H14N2O2: 218.1; found 219.0 (M+1)+.

Workup

temperatureAfter cooling to room temperature
extractionthe mixture is extracted with ethyl acetate (50 mL)
washThe organic layer is washed with saturated NaHCO3 (50 mL)
dry with materialdried over Na2SO4
customThe product is purified by flash chromatography (20-50% ethyl acetate in n-heptane)

Sources & evidence

ORD record: ord-14c6608861104155b133e6c2225fbc77
Source dataset: uspto-grants-2008_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07361671B2

Reaction notes

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