Method for synthesizing tranylcypromine intermediate
A technology of tranylcypromine and a synthetic method, applied in directions such as organic chemistry methods, chemical instruments and methods, amino compound preparation, etc., can solve problems such as expensive chiral oxazaborolane, trivial operation steps, waste of raw materials, etc., and achieve improvement. The synthesis route, the process steps are simple, and the cost is low.
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[0017] In the embodiment of the present invention, the synthetic method of tranylcypromine intermediate includes:
[0018] Substitution reaction of substituted aromatic ketone or multi-substituted aromatic ketone under the action of sodium nitrite, sodium iodide and reaction solvent to synthesize compound I;
[0019]
[0020] Compound I is subjected to a copper-hydrogen catalytic reaction under the action of a metal precursor, a ligand, and a catalyst to generate compound II, and the reaction is as follows:
[0021]
[0022] Under the action of compound II with DIAD and triphenylphosphine, compound III is generated, and the reaction is as follows:
[0023]
[0024] With compound III under the effect of zinc powder or iron powder, generate tranylcypromine intermediate, react as follows:
[0025]
[0026] Wherein, above-mentioned R1, R2 are all selected from F, Cl, Br, I, CH 3 , H, CH 3 O, Ph, C (CH 3 ) 3 One of them; the above R3 is selected from one of Cl and ...
Embodiment 1
[0054] Embodiment 1: the preparation of chlorine band difluoropropiophenone
[0055] Dissolve difluorobenzene (4.56g, 40mmol) and aluminum trichloride (5.65g, 42.4mmol) in dichloromethane (20ml), slowly add acid chloride (5.33g, 42mmol) dropwise at room temperature, and stir at room temperature for 0.5h , heated to 38°C, reacted for 30 hours, and monitored by TLC. Post-treatment: Cool the reaction system in an ice bath, then pour the reactant into frozen water to quench. Use dichloromethane to extract twice (50ml x 3), (or spin dry dichloromethane directly, use ethyl acetate (50ml x 3) to extract), combine organic phase, add 20ml saturated sodium bicarbonate solution to wash, combine organic phase Mutually. Dry over anhydrous sodium sulfate and spin dry. Pass through a silica gel column (PE:EA=15:1).
[0056] Characterization data: 1 H NMR (400 MHz, Chloroform-d) δ 7.88–7.69 (m, 2H), 7.38–7.19 (m, 1H), 3.91 (t, 2H), 3.42 (t, 2H).
Embodiment 2
[0057] Embodiment 2: the preparation of compound I
[0058] Chlorodifluoropropiophenone (3.07g, 15mmol), sodium nitrite (2.07g, 30mmol), and sodium iodide (45mg, 0.3mmol) were successively added to 20ml of acetone. Stirred at room temperature for 24h, monitored by TLC. Post-processing: spin dry acetone, add 100ml of water, extract with ethyl acetate (50ml x3), combine the organic phase, add 50ml of saturated saline, separate the organic phase, add anhydrous sodium sulfate to dry, spin dry, pass through silica gel Column (PE; EA=10:1 to 5:1), absolutely not using alumina to pass through the column, the yield obtained was 98%.
[0059] Characterization data: 1 H NMR (400 MHz, Chloroform-d) δ 7.89–7.70 (m, 2H), 7.38–7.19 (m, 1H), 4.83 (t, 2H), 3.62 (t, 2H).
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