3,7-disubstituted-trans-dicyclo[3,3,0] octane compound and its preparation and use
A compound, two-substituted technology, used in chemical instruments and methods, organic chemistry, instruments, etc.
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Embodiment 1
[0082] This example relates to the synthesis of the intermediate 7,7-ethylenedioxy-3-trans-bicyclo[3.3.0]octanone.
[0083] 1) Synthesis of trans-bicyclo[3.3.0]octane 3,7-dione
[0084] Add 5.3 g of NaOH and 95 ml of anhydrous methanol into a 250 ml Erlenmeyer flask, stir until the NaOH is completely dissolved, and filter to obtain a NaOH / anhydrous methanol solution. Add 22.5 grams of dimethyl acetone dicarboxylate in a 250 ml three-necked flask, N 2 Under protection, NaOH / anhydrous methanol solution was added with stirring, a white solid precipitated out, and heated to reflux until the solid dissolved. 9.4 ml of 40% glyoxal aqueous solution was added dropwise, and the addition was completed in 25 minutes, and a solid precipitated out, then heated to reflux for 10 minutes, cooled to room temperature, filtered to obtain a yellow solid, which was washed twice with 50 ml of cold methanol.
[0085] A solution of 21 ml of 37% hydrochloric acid and 60 ml of water and a yellow so...
Embodiment 2
[0090] Synthesis of 3,3-Ethylenedioxy-7-(3′,5′-difluorophenyl)-trans-bicyclo[3.3.0]octane
[0091] The reaction process is as follows:
[0092]
[0093]In the there-necked flask of 250 milliliters, add 3 grams of magnesium chips and 20 milliliters of anhydrous tetrahydrofuran, in the dropping funnel of 100 milliliters, add the solution of 22 grams of 3,5-difluorobromobenzene (99.7%) and 40 milliliters of anhydrous tetrahydrofuran, 5 mL of the solution was added dropwise to initiate the reaction. Slowly add the tetrahydrofuran solution dropwise, maintaining a slight reflux. After dropping, heat to reflux for 1 hour until almost all the magnesium chips disappear. A solution of 18 g of 7,7-ethylenedioxy-3-trans-bicyclo[3.3.0]octanone and 40 ml of tetrahydrofuran was added dropwise, and the mixture was refluxed for 2 hours. Cool down to about 0°C. Add 24 ml of 6M hydrochloric acid dropwise, control the temperature below 30°C, and hydrolyze for half an hour. Poured into wat...
Embodiment 3
[0125]
[0126] Synthesis of 3-oxo-7-(3′,4′-difluorophenyl)-trans-bicyclo[3.3.0]octane
[0127] Add 20 grams of 3,3-ethylenedioxy-7-(3',4'-difluorophenyl)-trans bicyclo[3.3.0]octane obtained in Example 2 to a 500-ml one-port bottle, 600 mL 88% formic acid, 200 mL toluene, stirred at room temperature for 12 hours, separated, washed the toluene layer with water until neutral, anhydrous Na 2 SO 4 Dry for 4 hours, filter and distill off the solvent to obtain 16.15 g of 3-oxo-7-(3',4'-difluorophenyl)-trans-bicyclo[3.3.0]octane, with a melting point of 44°C and a gas phase purity of 99.7 %.
[0128] The compound (b-n) that obtains with reference to above-mentioned same method hydrolysis embodiment 3 obtains following compound:
[0129] 3-Oxo-7-(3′,5′-difluorophenyl)-trans-bicyclo[3.3.0]octane
[0130]
[0131] 3-Oxo-7-(4′-fluorophenyl)-trans-bicyclo[3.3.0]octane
[0132]
[0133] 3-Oxo-7-(4′-methylphenyl)-trans-bicyclo[3.3.0]octane
[0134]
[0135] 3-Oxo-7-(4'-but...
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