Oxalyl chloride → 5-cyano-4-fluoro-2-methoxy-N-(3-nitro-benzyl)-benzamide

Temperatur

40 °C

To a stirring slurry of 5-cyano-4-fluoro-2-methoxy-benzoic acid (1.92 g, 9.8 mmol) in dichloromethane (20 mL, 0.5 M) was added oxalyl chloride (2.57 mL, 29.5 mmol) and DMF (1 drop). The mixture was heated to 40° C. until the solution was clear (1–2 h). Next, the mixture was allowed to cool to room temperature, concentrated under reduced pressure, and then diluted with dichloromethane (20 mL, 0.5 M). To the stirring mixture at 0° C. was added diisopropylethyl amine (4.3 mL, 24.6 mmol) followed by 3-nitrobenzylamine hydrochloride salt (2.78 g, 14.8 mmol). The stirring under nitrogen, the solution was gradually warmed to room temperature and stirred overnight. The mixture was then diluted with dichloromethane and washed with 2N HCl (3×25 mL) and saturated aq NaCl (2×25 mL). The organic layer was dried over Na2SO4, filtered, and concentrated to afford a yellow oil. Purification by MPLC (10–100% ethyl acetate in heptane, 23 mL/min, 75 min) provided [5-cyano-4-fluoro-2-methoxy-N-(3-nitro-benzyl)-benzamide (2.0 g, 63%) as a yellow solid: 1H NMR (DMSO-d6, 300 MHz) δ 8.55 (d, J=7.5 Hz, 1 H), 8.19 (9, 1 H), 8.15 (d, J=8.4 Hz, 1 H), 7.96 (bd s, 1 H), 7.70 (d, J=6.3 Hz, 1H), 7.54 (t, J=8.0 Hz, 5 H), 6.86 (d, J=10.5 Hz, 1 H), 4.76 (d, J=5.4 Hz, 1H), 4.07 (d, J=1.2 Hz, 3 H).

1. custom(1–2 h)
2. temperatureto cool to room temperature
3. concentrationconcentrated under reduced pressure
4. additiondiluted with dichloromethane (20 mL, 0.5 M)
5. temperatureThe stirring under nitrogen, the solution was gradually warmed to room temperature
6. washwashed with 2N HCl (3×25 mL) and saturated aq NaCl (2×25 mL)
7. dry with materialThe organic layer was dried over Na2SO4
8. filtrationfiltered
9. concentrationconcentrated
10. customto afford a yellow oil
11. customPurification by MPLC (10–100% ethyl acetate in heptane, 23 mL/min, 75 min)

ORD-Eintrag

ord-ac8d3575f97b4a8188d98dc2da407ecb

Quelldatensatz

uspto-grants-2007_03

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07189749B2