(2-methoxy-5-nitrophenyl)methanol

25016-02-8

5804-49-9

General procedure for the synthesis of (2-methoxy-5-nitrophenyl)methanol from 2-methoxy-5-nitrobenzaldehyde: Intermediate 312B (410 mg, 2.263 mmol) was dissolved in a solvent mixture of toluene (11.500 mL) and THF (11.50 mL) and cooled to -78 °C under nitrogen protection. DIBAL-H (1.0 M toluene solution, 3.40 mL, 3.40 mmol) was slowly added dropwise to the cooled solution. After the initial bubbles disappeared, the reaction mixture was gradually warmed to room temperature. After 1 hour of reaction, the mixture was cooled again to 0 °C and the reaction was quenched with 1.0 M HCl. The resulting suspension was stirred vigorously for 45 min to ensure complete decomposition of the aluminate complex. Subsequently, the reaction mixture was diluted with EtOAc and extracted. The organic phase was washed with brine, dried over anhydrous MgSO4, filtered and concentrated. The crude product was purified by ISCO fast chromatography (80 g silica gel column, elution gradient 0-100% EtOAc/hexane, 33 min, 50% product collected) to afford intermediate 312C (370 mg, 1.717 mmol, 76% yield) as a light yellow solid.LC-MS analysis (Method H): retention time RT = 0.68 min, MS ( ESI) m/z: 184.0 ([M + H]+).1H NMR (400 MHz, chloroform-d) δ 8.29 (d, J = 2.9 Hz, 1H), 8.21 (dd, J = 9.0, 2.6 Hz, 1H), 6.94 (d, J = 9.0 Hz, 1H), 4.75 (d, J = 6.4 Hz, 2H), 3.97 (s 3H), 2.07 (t, J = 6.4 Hz, 1H).