Water → 2-[1-(Hydroxymethyl)cyclopropyl]-3-(methoxymethoxy)-6-methyl-phenol

Participants

Reaction Conditions

Reaction Steps

To a solution of 1-[2,6-bis(methoxymethoxy)-3-methyl-phenyl]cyclopropanecarbonitrile (Intermediate 35, 26.2 g, 94.476 mmol) in Methanol (260 mL) hydrogen chloride 6N in water (31.5 ml, 188.95 mmol) was added and the reaction mixture was stirred for 5 hours at 70° C. Volatiles were removed under reduced pressure and the residue was suspended in Toluene (50 ml) and the solvent evaporated. Additional Toluene (50 ml) was added and then re-evaporated. The residue (yellow pale solid) was dissolved in THF (200 mL) and the reaction mixture was cooled to 0° C. chloro(methoxy)methane (7.89 ml, 103.92 mmol) was added followed by a portionwise addition of sodium hydride 60% dispersion in mineral oil (4.1569 g, 103.92 mmol). The reaction mixture was stirred for 1 hour at the same temperature and then lithium aluminum hydride 1M in THF (47.24 ml, 47.24 mmol) was slowly added. The reaction mixture was stirred for 1 hour at 0° C. and then it was quenched with ice cold aqueous 2N HCl (100 ml), diluted with water (200 ml) and extracted with ethyl acetate (2×200 ml). The organic layer was dried (Na2SO4), filtered and evaporated and The residue was purified by flash chromatography on silica gel using a silica pad ˜300 g of silica and cyclohexane/ethyl acetate from 100:0 to 70:30 as eluent affording the title compound (16.4 g) as colourless oil.

Provenance & Evidence