Sulfuric Acid → 2-(tert-Butyldimethylsilyl)-N,N-dimethyl-1H-imidazole-1-sulfonamide

Participants

Reaction Conditions

Reaction Steps

7-Methoxy-1-tetralone (1) (1.5 g, 8.5 mmol) and 1-dimethylsulfamoyl-2-t-butyldimethylsilyl-5-imidazolecarboxaldehyde (2) (2.7 g, 8.5 mmol) were added to 8.5 mL of a 40% solution of sulfuric acid. The reaction was heated for 24 h at 90° C. After cooling to rt, the reaction was made basic with excess concentrated ammonium hydroxide. The mixture was extracted twice with THF. The organic layers were combined and washed with brine. The organic layer was separated and dried over sodium sulfate. The mixture was filtered and the filtrate concentrated under reduced pressure to afford 2.7 g of a yellow solid (3) comprising 3-(3H-imidazole-4(5)ylmethylene)-7-methoxy chroman-4-one. The crude product was suspended in 100 mL of ethanol and a palladium on carbon catalyst (10%, 0.27 g) added. The mixture was shaken in a Parr hydrogenator apparatus while under 40 psi of hydrogen. After 19 h the reaction mixture was filtered through Celite and the filtrate concentrated under reduced pressure. Column chromatography with 7% methanol in chloroform afforded 1.05 g (46%) of a tan color solid comprising 2-[3H-Imidazole-4(5)-ylmethyl]-7-methoxy-3,4-dihydro-2H-naphthalen-1-one (4)(B-1a). (4) (0.5 g, 1.95 mmol) was added to 20 mL of methanol. Sodium borohydride (74 mg, 1.95 mmol) was added to the solution. After stirring for 2.5 h at rt the reaction mixture was quenched with water. The reaction mixture was then extracted twice with ethyl acetate. The organic layers were combined and washed with brine. The organic layer was separated and dried over sodium sulfate. The mixture was filtered and the filtrate concentrated under reduced pressure to afford 0.5 g of a white solid (5) comprising 2-[3H-Imidazole-4(5)-ylmethyl]-7-methoxy-3,4-dihydro-2H-naphthalen-1-ol. The crude product was dissolved in 26 mL of dichloromethane. Triethylsilane (2.5 mL, 15.6 mmol) and trifluoroacetic acid (4.8 mL, 62.3 mmol) were added and the reaction stirred at rt for 22 h. The reaction was made basic with 2N NaOH and the organic layer separated and washed with brine. The solution was dried over sodium sulfate. The mixture was filtered and the filtrate concentrated under reduced pressure. Column chromatography with 7% methanol in chloroform afforded 0.39 g (83%) of a tan color oil (6). The product was dissolved in methanol and an excess of hydrogen chloride (HCl) in ether was added. The solution was concentrated under reduced pressure to yield 0.3 g of a tan color solid. Column chromatography with 7% methanol in chloroform afforded 0.25 g (46%) of 4(5)-(7-methoxy-1,2,3,4-tetrahydronaphthalen-2-ylmethyl)-1H-imidazole, hydrogen chloride salt (B-1) as white crystals (7) after recrystallization from a mixture of acetone and methanol.

Provenance & Evidence