Chloromethyl Methyl Ether → Methoxymethyl 3-nitrophenyl ether

Participants

Reaction Conditions

Reaction Steps

A solution of 3-nitrophenol (5.00 g, 36 mmol) in 100 mL of anhydrous DMF at 0° C. was treated with NaH (2.16 g 54 mmol) in several portions over 5 min. After 10 min, Bu4NI (1.33 g, 3.6 mmol) was added and followed by dropwise addition of ClCH2OCH3 (4.1 mL, 54 mmol). The reaction mixture was stirred at 25° C. for 21 h before being quenched with the slow addition of 100 mL of H2O. The aqueous layer was extracted with EtOAc (3×100 mL). The organic layers were combined, washed with 10% aqueous NaHCO3 (100 mL), H2O (4×50 mL), dried (Na2SO4), and concentrated under reduced pressure. Flash chromatography (SiO2, 4×15 cm, 10% EtOAc/hexane) provided 11 (5.83 g, 89%) as a pale yellow solid: 1H NMR (CDCl3, 250 MHz) δ 7.86 (m, 2H), 7.34 (m, 2H), 5.22 (s, 2H), 3.46 (s, 3H); 13C NMR (CDCl3, 62.5 MHz) δ 157.5, 148.9, 129.9, 122.6, 116.5, 110.9, 94.4, 56.1; IR (film) νmax 3099, 2959, 2829, 1619, 1584, 1537, 1349, 1237, 1153, 1081 cm−1; FABHRMS (NBA/NaI) m/z: 206.0430 (C8H9NO4+Na+ requires 206.0429). Anal. Calcd for C8H9NO4: C, 52.46; H, 4.95; N, 7.65. Found: C, 52.37; H, 4.89; N, 7.61.

Provenance & Evidence