With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.954236-44-3,tert-Butyl 3-oxo-1-oxa-8-azaspiro[4.5]decane-8-carboxylate,as a common compound, the synthetic route is as follows.,954236-44-3
tert-butyl ORSVS-O-chloro-delta-fluorophenvD-i-oxa-delta-azaspiro^.deltaldecane-delta-carboxylate To a solution of tert-butyl 3-oxo-1-oxa-8-azaspiro[4.5]decane-8-carboxylate (3.01 g, 11.8 mmol) in 2-MeTHF (100 imL) at 0 0C was added 3-chloro-delta-fluorophenylmagnesium bromide (0.5 M in THF, 25 ml_, 12.5 mmol; Aldrich) dropwise. After 30 min the reaction was warmed to RT for 2 hrs, and then stored in the freezer for 2 days. More 3-chloro-5-fluorophenylmagnesium bromide (27 ml_, 13.5 mmol) was added at 0 0C. After stirring overnight at RT, the reaction was quenched with saturated ammonium chloride and extracted with ethyl acetate. The organic layers were dried over magnesium sulfate, filtered, and concentrated to give crude tert- butyl (3RS)-3-(3-chloro-5-fluorophenyl)-3-hydroxy-1-oxa-8-azaspiro[4.5]decane-8-carboxylate as an oil. A solution of the crude alcohol and triethylsilane (9.42 ml_, 59 mmol, 5 equiv) in methylene chloride (100 ml_) was treated with borontrifluoride diethyl etherate (2.91 ml_, 23.6 mmol, 2 equiv) and trifluoroacetic acid (4.38 ml_, 59 mmol, 5 equiv) at 0 0C. After stirring overnight at RT, the reaction mixture was concentrated. The residue was dissolved in ethyl acetate and the organic was treated with 2.5 N NaOH (40 ml_) and water (50 ml_). The layers were separated and the aqueous layer was extracted with ethyl acetate (3 x 50 ml_). The combined organic layers were dried over magnesium sulfate, filtered, and concentrated to give 3.27 g of an oil. To the oil in 2-MeTHF (25 ml_) was added Boc anhydride (1.8Og, 8.26 mmol), DMAP (cat.), and triethylamine (2.47 ml_, 17.7 mmol) and the mixture was stirred overnight. The mixture was treated with water (50 ml_) and 1 N HCI (20 ml_) and extracted with ethyl acetate (3×100 ml_). The organic was dried over magnesium sulfate, filtered and evaporated to give an oil. The oil was purified by flash chromatography (0- 30% EA/heptane) to give the title compound as a solid (0.42 g, 10%). m/z 314 (MH+ minus tBu).
The synthetic route of 954236-44-3 has been constantly updated, and we look forward to future research findings.
Reference£º
Patent; PFIZER INC.; LONG, Scott Allen; MEYERS, Marvin Jay; PELC, Matthew James; SCHWEITZER, Barbara Ann; THORARENSEN, Atli; WANG, Lijuan Jane; WO2010/58318; (2010); A1;,
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