Method for preparing 3-(4-fluorophenyl)-4-benzyl-2-molindone
A technology of morpholinone and fluorophenyl, which is applied in the field of preparation of neurokinin receptor blockers aprepitant and 3--4-benzyl-2-morpholinone, can solve the problem of unsuitable Large-scale industrial production and other issues, to achieve the effect of cheap raw materials, high yield, and low cost
- Summary
- Abstract
- Description
- Claims
- Application Information
AI Technical Summary
Problems solved by technology
Method used
Image
Examples
Embodiment 1
[0026] Embodiment 1: the preparation of 4-benzylmorpholine
[0027] In a 500 ml three-necked flask, mechanically stirred, put in morpholine (17.4 g, 200 mmol), 150 ml of acetonitrile, and 5 ml of triethylamine, cooled to below 10°C, and slowly added dropwise benzyl bromide (28.5 g, 166 mmol) under stirring. , the drop was completed, raised to 80°C, and reacted for 4 hours, and the reaction was monitored by TLC. The solution was poured into 500 ml of ice water, extracted with dichloromethane (2*250 ml), the organic layer was washed with saturated sodium bicarbonate solution, dried over anhydrous magnesium sulfate, filtered, and the solvent was evaporated under reduced pressure. Obtain 25 grams of light yellow oil, yield 85%, ( 1 HNMR, 300MHz, internal standard TMS, solvent CDCl 3 ) as follows: δppm 7.33-7.45 (m, 5H, Ar-H), 3.95 (t, 4H, CH 2 -O-CH 2 ),3.37(s,2H,CH 2 ),2.84(t,4H,CH 2 -N-CH 2 ).
Embodiment 2
[0028] Embodiment 2: the preparation of N-benzyl-2-morpholinone
[0029] 250 ml round bottom flask, mechanically stirred, 4-benzylmorpholine (9 g, 50 mmol) obtained in the previous step, 100 ml of acetonitrile, stirred evenly, added 1.6 g of N-hydroxyphthalimide, and passed through oxygen React for 8 hours, control the temperature not to exceed 60°C, monitor the completion of the reaction by TLC, pour the solution into 100 ml of ice water, extract with ethyl acetate (3*100 ml), dry over anhydrous sodium sulfate, filter, and evaporate the solvent under reduced pressure , Obtain 8 grams of light yellow oily substance, yield 83%. ( 1 HNMR, 300MHz, internal standard TMS, solvent CDCl 3 ) as follows: δppm 7.35-7.45 (m, 5H, Ar-H), 3.98 (t, 4H, CH 2 -O),3.69(s,2H,CH 2 ),3.35(s,2H,CH 2 ),2.94(t,2H,CH 2 ).
Embodiment 3
[0030] Example 3: Preparation of 3-(4-fluorophenyl)-4-benzyl-2-morpholinone
[0031] In a 250ml round bottom flask, stir mechanically, mix p-fluorobromobenzene (10.5g, 60mmol) with 100ml ethanol, add 0.68g sodium ethoxide, stir to dissolve, cool down to below 10°C, slowly add N-benzyl - 2-Morpholinone (5.7 g, 30 mmol), after dropping, the temperature was raised to reflux, and the reaction was carried out for 6 hours, and the completion of the reaction was monitored by TLC. The solvent was evaporated to dryness under reduced pressure, 50 ml of saturated sodium bicarbonate solution was added to the residue, mixed evenly, extracted with dichloromethane, the organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and evaporated to dryness to obtain 6.6 g of light yellow oil, Yield 77%. ( 1 HNMR, 300MHz, internal standard TMS, solvent DMSO-d6) as follows: Ar-H),5.15(s,1H,CH),4.24(s,2H,CH 2 ),3.35(t,2H,CH 2 ), 2.86(t,2H,CH 2 ).
PUM
Login to View More Abstract
Description
Claims
Application Information
Login to View More