Preparation method of 2-aryl cyclopropylamine compound
A technology of arylcyclopropylamine and compound, which is applied in the field of preparation of 2-arylcyclopropylamine compound, can solve the problems of low efficiency of ACPA and unavailability of multi-substituted ACPA, and achieve high stereoselectivity and simple route High efficiency and mild reaction conditions
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[0039] The present invention provides a kind of preparation method of 2-arylcyclopropylamine compound, and this method comprises:
[0040] Add organic solvent into the reaction vessel, then add copper catalyst and ligand in sequence, preferably stir at room temperature for 2-3min, then add alkali, preferably stir at room temperature for 2-3min, then add boric acid ester, preferably stir at room temperature 2-3min, and finally add cyclopropene compound and hydroxylamine-O-benzoic acid ester to react, preferably at -50-40°C and stir for 40-180min to obtain 2-arylcyclopropylamine compound.
[0041] According to the present invention, the ligand is a bidentate phosphine ligand dppbz, which is obtained commercially; the structure of the bidentate phosphine ligand is shown in L1:
[0042]
[0043] According to the present invention, the organic borate compounds include pinacol esters or neopentyl glycol esters of aryl, heteroaryl or alkenyl boronic acids, more preferably 2-naphth...
Embodiment 1
[0055] In a 25 ml reaction tube, tetrahydrofuran was added as a solvent (2 ml), followed by adding cuprous chloride (0.010 mmol), dppbz L1 (5.4 mg, 0.06 mmol), stirring at room temperature for 2 min; adding m-CPBA (2 mg, 0.01 mmol), sodium tert-butoxide (28.8 mg, 0.3 mmol) was stirred for 2 min; then 2-naphthalene borate neopentyl glycol ester (57.6 mg, 0.24 mmol) of 1.2 times the molar mass of the substrate was stirred for about 2 min Add 3-methyl-3-phenylcyclopropene (0.2 mmol), benzoyloxymorpholine (50mg, 0.24 mmol) reaction system is placed on stirring at room temperature, TLC spot plate monitoring, after the reaction is complete, pass through column Purified by chromatography to obtain an oily liquid, which was subjected to 1 H NMR (such as figure 1 ), 13 C NMR (eg figure 2 shown), the structure is determined to be formula 1, the weighed weight is 68 mg, the calculated yield is 99%, dr=93:7, figure 1 Proton NMR spectrum; the reaction can be represented by the followi...
Embodiment 2
[0058] In a 25 ml reaction tube, tetrahydrofuran was added as a solvent (2 ml), followed by adding cuprous chloride (0.010 mmol), dppbz L1 (5.4 mg, 0.06 mmol), stirring at room temperature for 2 min; adding m-CPBA (2 mg, 0.01 mmol), sodium tert-butoxide (28.8 mg, 0.3 mmol) was stirred for 2min; then neopentyl glycol 4-trifluoromethylphenyl borate (62 mg, 0.24 mg mol), stirred for about 2min; added 3-methyl-3-phenylcyclopropene (0.2 mmol), benzoyloxymorpholine (50 mg, 0.24 mmol) and the reaction system was stirred at room temperature, monitored by TLC spot plate, After the reaction was complete, it was separated and purified by column chromatography to obtain an oily liquid, which was subjected to 1 H NMR (such as image 3 shown), 13 C NMR (eg Figure 4 shown), the structure is determined to be formula 2, the weighed weight is 56 mg, the calculated yield is 78%, dr=92:8; image 3 Proton NMR spectrum; the reaction can be represented by the following equation:
[0059]
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