Hydrochloric Acid → HCID 71231034, compound

Participants

Reaction Steps

To a mixture of 104 g (0.407 mmol) of 4-bromo-7-methoxy-2-methylindan-1-one and 15.0 g (0.397 mmol) of NaBH4 in a mixture of 410 ml of THF 205 ml of methanol was added dropwise with vigorous stirring for 4 h at +5° C. This mixture was stirred overnight at room temperature and then added to 1 liter of cold water. The resulting mixture was carefully acidified by 2 M HCl to pH 5.0, and the formed indan-1-ol was extracted with 500 ml of dichloromethane. The aqueous layer was additionally extracted with 2×200 ml of dichloromethane. The combined organic extract was evaporated to dryness. To the resulting yellowish liquid of the crude 4-bromo-7-methoxy-2-methylindan-1-ol 800 ml of DMSO, 92.0 g (1.64 mol, 4.0 eq) of KOH, and 116 g (0.817 mol, 2.0 eq) of MeI were added. This mixture was stirred for 3 h at ambient temperature and then added to 3 L of cold water. The crude product was extracted with dichloromethane (500 ml, then 3×250 ml). The combined organic extract was washed 5 times by 1 liter of water and then evaporated to dryness. The product was isolated by flash chromatography on silica gel 60 (40-63 μm; eluent: hexanes-dichloromethane=2:1, then 1:2 and, finally, 1:5, vol.) followed by rectification in vacuum, 149-154° C./8 mm Hg. Yield 96.0 g (87%) of a ca. 1 to 2 mixture of two diastereomers.

Provenance & Evidence