Methyl morpholine oxide → 2-Methoxybenzaldehyde

Participants

Reaction Steps

A solution of crude 21 (12.2 g, ˜25 mmol, 1.0 equiv), 4-methylmorpholine N-oxide (3.5 g, 30 mmol, 1.2 equiv) in DCM (150 mL) was cooled to ˜7° C. and tetrapropylammonium perruthenate (TPAP) (0.2 g, 0.5 mmol, 2 mole %) was added. The mixture was allowed to warm to room temperature and stirred. After 1 hr TLC showed the reaction was incomplete. Additional TPAP (0.2 g) was added and the mixture stirred overnight at room temperature. Although unoxidized 21 remained, the mixture was filtered through Celite, washing the Celite pad with DCM. The filtrate was concentrated under reduced pressure to give a brown oil. The crude product was absorbed onto silica gel using DCM and dry-loaded on a column of silica gel (125 g) packed in heptanes. The column was eluted with heptanes (750 mL), 5% EtOAc/heptanes (1000 mL), 10% EtOAc/heptanes (1000 mL) and 15% EtOAc/heptanes (1000 mL). Clean separation of 22 from 21 was not achieved. All fractions containing 22 and 21 were concentrated under reduced pressure to give a pale yellow oil. The mixture was dissolved in DCM (300 mL) and MnO2 (10.9 g, 125 mmol) was added. The mixture stirred overnight at room temperature, then refluxed the following day for 6 hr. The mixture was filtered through Celite, washing the Celite pad with DCM (300 mL). The filtrate was concentrated under reduced pressure to give a pale yellow oil. The crude product was absorbed onto silica gel using DCM and dry-loaded on a column of silica gel (125 g) packed in heptanes. The column was eluted with heptanes (500 mL) and 5% EtOAc/heptanes (3000 mL). Product fractions were concentrated under reduced pressure and the residue dried under high vacuum for 2 hr to give 7.5 g (77% for 2 steps from 1) of 22 as a colorless oil.

Provenance & Evidence