Methyl iodide → 2-Methoxy-4-(2-tetrahydropyranyl)oxy-6-methylbenzaldehyde

Participants

Reaction Steps

An ice-cold yellow solution of 2-hydroxy-6-methyl-4-(tetrahydro-pyran-2-yloxy)-benzaldehyde (7.60 g, 32.17 mmol) in DMF (150 mL), was treated with NaH (0.93 g, 38.63 mmol) in portions over 30 min. The suspension was stirred for 15 min, then methyl iodide (3.0 mL, 48.09 mmol) was added dropwise. The mixture was warmed to rt, stirred for 1 h, then quenched with water and extracted with EtOAc. The extracts were washed with brine, dried (Na2SO4), filtered and concentrated to a yellow liquid. The crude product of 2-methoxy-6-methyl-4-(tetrahydro-pyran-2-yloxy)-benzaldehyde was used in the next step without further purification. 1H NMR (400 MHz, CDCl3) δ 10.49 (s, 1H), 6.50 (s, 1H), 6.49 (s, 1H), 5.54-5.52 (m, 1H), 3.87 (s, 1H), 3.88-3.80 (m, 1H), 3.67-3.61 (m, 1H), 2.57 (s, 3H), 2.10-1.95 (m, 1H), 1.95-1.82 (m, 2H), 1.80-1.58 (m, 3H).

Provenance & Evidence