1,2-Dihydro-6,7-dimethoxy-3-nitronaphthalene → 5-(1,2,3,4-Tetrahydro-6,7-dimethoxy-2-nitro-1-naphthyl)-2-propyl-4-(((2-tetrahydropyranyl)oxy)methyl)oxazole

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Reaction Conditions

Reaction Steps

n-Butyllithium (2.5M in hexane, 10 mmol) was added to a solution of the compound from step 29c (2.70 g, 8.88 mmol) in 40 mL of THF cooled to -78° C. The resulting yellow solution was stirred for 30 min at -78° C., and a solution of 1,2-dihydro-6,7-dimethoxy-3-nitronaphthalene (2.227 g, 9.48 mmol), from Example 1b, precooled to -78° C., was added via cannula. The reaction was stirred for 2 hours at -78° C., then the reaction was quenched by the addition of 10 mL of satd. NH4Cl. After warming to room temperature, the organic layer was separated, and the aqueous layer was extracted with 2×50 mL of methylene chloride. The organics were combined, dried over MgSO4 and concentrated. The crude product was dissolved in 45 mL of methanol and treated with 8 mL of triethylamine. This solution was stirred for 15 hours at room temperature. The solvent was removed under reduced pressure, and the residue was chromatographed on silica gel, eluting with 30-60% ethyl acetate in hexane, to afford after removal of the solvent and drying, 3.64 g (89% yield) of the title product as an oil. MS: 461 (M+H)+. NMR showed a mixture of diastereomers.

Provenance & Evidence