Compound for preparing ramelteon, preparation method thereof and application thereof

[0060] Preparation of (1,6,7,8-tetrahydro-2H-indeno-[5,4-b]furan-8-ylidene)acetonitrile (2)

[0061] Add 21.27 g (0.12 mol) of diethyl cyanomethylene phosphonate, 1,2,6,7-tetrahydro-8H-indeno-[5,4-b]furan-8-one in sequence in the reaction flask 17.42g (0.10mol), 120ml of toluene and 60ml of deionized water, after stirring at room temperature, add 1.62g (0.005mol) of tetrabutylammonium bromide and 20.70g (0.15mol) of anhydrous potassium carbonate, and heat up to 60-70 ℃, keep stirring and react for 8 hours; after the reaction, cool to room temperature, separate the toluene layer, extract the water layer with 30ml of toluene, combine the toluene solution, wash with 25ml of saturated NaCl aqueous solution, evaporate the solvent under reduced pressure, and recrystallize the residue with methanol , to obtain 17.20 g of light yellow crystalline solid, mp: 146-148°C, yield 87.2%.

[0063] Preparation of (1,6,7,8-tetrahydro-2H-indeno-[5,4-b]furan-8-ylidene)acetonitrile (2)

[0064] Add 40.54 g (0.12 mol) of cyanomethylenetriphenylphosphonium chloride, 1,2,6,7-tetrahydro-8H-indeno-[5,4-b]furan-8- Ketone 17.42g (0.10mol) and toluene 200ml, after stirring at room temperature evenly, put in an ice bath and cool to 0-5°C, add 15% sodium methoxide methanol solution (0.13mol) dropwise, remove the ice bath, and stir at room temperature React for 2.5h, add 100ml of deionized water to the reaction bottle, stir for 30min, pour the reaction solution into a separatory funnel, separate the organic layer, and wash with 40ml of saturated aqueous NaCl solution, evaporate the solvent under reduced pressure, and reconstitute the residue with methanol Crystallized to obtain 16.51 g of light yellow crystalline solid, mp: 145-148°C, yield 83.7%.

[0066] Preparation of methyl (1,6,7,8-tetrahydro-2H-indeno-[5,4-b]furan-8-ylidene)acetate (3a)

[0067] The operation process is the same as in Example 1, except that diethyl cyanomethylene phosphonate is replaced with 2-(diethoxyphosphonic acid group) methyl acetate to obtain (1,6,7,8-tetrahydro-2H-indene And-[5,4-b]furan-8-ylidene)acetate methyl ester as light yellow oily liquid, yield 92.1%. It was directly used in the next reaction without further purification.