Water → 2-Hydroxy-4-nitrobenzonitrile

Temperature

150 °C

3,4-Methylenedioxynitrobenzene (1.67 g, 10.0 mmol) was dissolved in 20 mL of HMPA and sodium cyanide (0.49 g, 10.0 mmol) was added. The reaction was heated to 150° C. under nitrogen and three portions of sodium cyanide (0.245 g, 5.00 mmol, total) were added over 15 min. The reaction was maintained at 150° C. for 45 min, cooled, and poured into 50 mL of H2O followed by the addition of 50 mL of 5% NaOH. The aqueous layer was extracted with ether (2×25 mL) and the organic layer was discarded. The basic aqueous layer was carefully acidified to pH 4 by addition of 10% HCl and extracted with ether (3×25 mL). The combined organic layers were washed with brine (25 mL), dried over sodium sulfate and concentrated in vacuo. Purification by flash chromatography on silica gel eluting with 5% MeOH/CH2Cl2 gave 1.05 g (64%) of compound 477A as a yellow-brown solid. HPLC: 91.6% at 1.03 min (retention time) (Phenomenex column, 30×4.6 mm, 10-90% aqueous methanol over 2 min containing 0.1% TFA, 5 mL/min, monitoring at 220 nm. MS (ES): m/z 165.23 [M+H]+.

1. temperatureThe reaction was maintained at 150° C. for 45 min
2. temperaturecooled
3. extractionThe aqueous layer was extracted with ether (2×25 mL)
4. additionThe basic aqueous layer was carefully acidified to pH 4 by addition of 10% HCl
5. extractionextracted with ether (3×25 mL)
6. washThe combined organic layers were washed with brine (25 mL)
7. dry with materialdried over sodium sulfate
8. concentrationconcentrated in vacuo
9. customPurification by flash chromatography on silica gel eluting with 5% MeOH/CH2Cl2

ORD record

ord-d9c44d482dcf4fe28cf913841e958172

Source dataset

uspto-grants-2010_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07655689B2