1,6-Dioxaspiro[2.5]octane

Trimethylsulfoxonium iodide (286 mg, 13 mmol) was dissolved in DMSO (20 mL) under an atmosphere of nitrogen. NaH (60percent dispersion in mineral oil, 520 mg, 13 mmol) was then added portion-wise (NB. vigorous effervescence observed). The resultant suspension was stirred at rt for 1 h whereupon tetrahydro-4/-/-pyran-4-one 1-107 (0.93 mL, 10 mmol) was added dropwise. The reaction mixture was stirred at rt for an additional 1 h where it was then poured into a water / ice slurry. The aqueous phase was extracted with Et.20 (x 3) and the combined organic extracts washed with water and brine before drying over MgSC>4. Concentration in vacuo provided the title compound as a pale yellow oil (725 mg, 6.3 mmol, 63percent).A suspension of trimethylsulfoxonium iodide (28.6 g, 130 mmol) in DMSO (200 mL) in two neck RBF (500 mL) at room temperature, NaH (5.19 g, 130 mmol, 60percent in mineral oil) was added in portions under N2 pressure. Stirring was continued for one hour, then a solution of dihydro-2H-pyran-4(3H)-one (10 g, 100 mmol) in DMSO (10 mL) was added dropwise over 5 min. The reaction mixture was stirred at room temperature for 1 hr, then poured into ice-water (300 mL) and extracted with Et20 (2 x 200 mL). The organics were washed with water and brine, dried over MgSO4, filtered and concentrated to give 1, 6-dioxospiro[2.5]octane (4.9 g, 42.9 mmol, 43.0percent yield) as a colorless oil.Step 1: Trimethylsulfonium iodide (28.6 g, 130 mmol) in DMSO (200 mL) for two-neck RBF (500 mL)NaH (5.19 g, 130 mmol, 60percent in mineral oil) was added in portions to the suspension at room temperature under N2 pressure.Keep stirring for one hour, A solution of dihydro-2H-pyran-4(3H)-one (10 g, 100 mmol) in DMSO (10 mL) was then added dropwise over 5 min.The reaction mixture was stirred at room temperature for 1 hr.Then pour ice-water (300 mL) and use Et 2 O (2 x 200 mL)extraction. The organic liquid is washed with water and saline solution.Dry over MgSO 4 , filter, and concentrate.Get 1, 6-dioxaspiro[2.5]octane(4.9 g, 42.9 mmol, 43.0percent yield)Colorless oil.EXAMPLE H8: 4-r((2/?.5S)-44f3-r(5-fluoro-2-methylpyrimidin-4-yl)aminol-6.6- dimethyl^.β-dihvdropyrrolora^-cipyrazol-SdHWIlcarbonvD^.δ- dimethylpiperazin-1-yl)methyl1tetrahvdro-2H-pyran-4-ol; Intermediate H8(i): 1 , 6-dioxaspiro[2.5]octane; A solution of 4-methylenetetrahydro-2/-/-pyran (1.00 g, 10.2 mmol) in CHIntermediate HKi): 1 , 6-dioxaspiro[2.5]octaneA solution of 4-methylenetetrahydro-2H-pyran (1.00 g, 10.2 mmol) in CHUnder nitrogen 6.6 g sodiumhydride (60percent in mineral oil) are suspended in 90 ml tetrahydrofurane and cooled to 0° C. 91.7 Trimethylsulfonium iodide are added in portions. To this mixture a solution of 15 g dihydro-2H-pyran-4(3H)-one in 300 ml dimethylsulfoxide and 60 ml tetrahydrofurane is added dropwise. Afterwards the mixture is warmed to room temperature and stirred for 18 hours. The mixture is then poured into 1.2 l icewater and extracted for three times with diethylether. The combined organic phases are washed with brine and dried with sodium sulphate. Evaporation of the solvents in vacuo gives the product.Yield: 10.15 g (59percent of theory)RIntermediate 2: (S)-9-(tert-Butyldimethylsilyloxy)-4-isopropyl-9-hydroxy-, 7, 7-(ethan-1 , 2-diyl)-2', 3', 5', 6, 6', 7, 8, 9- octahydro-3H-spiro[furo[3, 4-c]quinoline-1 , 4'-pyran]-3-one Stepl : 1 , 6-Dioxaspiro[2.5]octane Under nitrogen 6, 6 g sodiumhydride (60percent in mineral oil) are suspended in 90 ml tetrahydrofurane and cooled to 0°C. 91 , 7 Trimethylsulfonium iodide are added in portions. To this mixture a solution of 15 g dihydro-2H-pyran-4(3H)-one in 300 ml dimethylsulfoxide and 60 ml tetrahydrofurane is added dropwise. Afterwards the mixture is warmed to room temperature and stirred for 18 hours. The mixture is then poured into 1 , 2 I icewater and extracted for three times with diethylether. The combined organic phases are washed with brine and dried with sodium sulphate. Evaporation of the solvents in vacuo gives the product. Yield: 10, 15 g (59 percent of theory) RStep 1: Step 1. Synthesis of Intermediate 6-2. To a mixture of trimethylsulfoxonium iodide (12.2 g, 59.8 mmol) in DMSO (40 mL) at 5 °C under N

Molecular Weight:114.14
XLogP3:0.1
Hydrogen Bond Acceptor Count:2
Exact Mass:114.068079557
Monoisotopic Mass:114.068079557
Topological Polar Surface Area:21.8
Heavy Atom Count:8
Complexity:94.7
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes