7,7-dimethyl-1,4-dioxaspiro[4.5]decan-8-one

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 7,7-dimethyl-1,4-dioxaspiro[4.5]decan-8-one (1.0 equiv.) in MeOH (0.5 M) was added sodium borohydride (1.0 equiv.) slowly at 0° C. under nitrogen, and the resulting reaction mixture was stirred at room temperature for 60 min. TLC (petroleum ether:ethyl acetate=10:1) showed that the reaction was completed. Water was added, and the solvent was removed under reduced pressure. The aqueous layer was extracted with DCM. The combined organic layers were washed with brine, dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated under vacuum to give 7,7-dimethyl-1,4-dioxaspiro[4.5]decan-8-ol (99% yield), which was used in the next step without further purification. 1H NMR (400 MHz, CDCl3) δ (ppm) 3.85-3.94 (m, 4H), 3.37-3.40 (m, 1H), 1.41-1.81 (m, 7H), 0.97 (s, 6H). the resulting reaction mixture the solvent was removed under reduced pressure The aqueous layer was extracted with DCM The combined organic layers were washed with brine dried over anhydrous sodium sulfate filtered The filtrate was concentrated under vacuum

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 1,4-dioxaspiro[4.5]decan-8-one (1.0 equiv.) in anhydrous THF (0.6 M) was added sodium hydride (2.0 equiv, 60% in mineral oil) at 0° C. under nitrogen. After the resulting reaction mixture was stirred at room temperature for 60 min, iodomethane (2.5 equiv.) was added. The reaction was stirred at 10° C. overnight. TLC (petroleum ether:ethyl acetate=10:1) showed that the reaction was completed. The reaction was quenched with saturated aqueous ammonium chloride solution and the aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with brine, dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated under vacuum, and the residue was purified by silica gel column chromatography (10% ethyl acetate in petroleum ether) to afford the 7,7-dimethyl-1,4-dioxaspiro[4.5]decan-8-one (40% yield) as colorless oil. 1H NMR (400 MHz, CDCl3) δ (ppm) 3.99 (s, 4H), 2.55-2.58 (m, 2H), 1.97-2.00 (m, 2H), 1.87 (s, 2H), 1.16 (s, 6H). After the resulting reaction mixture The reaction was stirred at 10° C. overnight The reaction was quenched with saturated aqueous ammonium chloride solution the aqueous layer was extracted with ethyl acetate The combined organic layers were washed with brine dried over anhydrous sodium sulfate filtered The filtrate was concentrated under vacuum the residue was purified by silica gel column chromatography (10% ethyl acetate in petroleum ether)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 7,7-Dimethyl-1,4-dioxaspiro[4.5]decan-8-one (2.8 g, 15.217 mmol, 1 eq) and 4-methoxy-benzylamine (2.08 g, 15.217 mmol, 1 eq) were dissolved in dichloromethane (100 ml) and stirred for 3 h at RT. Na(OAc)3BH (9.67 g, 45.65 mmol, 3 eq) was added in portions at 0° C., and stirring was carried out for 20 h at RT. The reaction solution was diluted with dichloromethane (100 ml), washed with water (100 ml) and sat. NaCl solution (100 ml), dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography (Alox neutral, 10% ethyl acetate in hexane). Yield: 46% (2.13 g, 6.98 mmol). stirring was carried out for 20 h at RT washed with water (100 ml) and sat. NaCl solution (100 ml) dried over sodium sulfate concentrated under reduced pressure The crude product was purified by column chromatography (Alox neutral, 10% ethyl acetate in hexane)