Synthetic method of 3-difluoromethyl piperidine hydrochloride and derivative thereof
A kind of technology of difluoromethylpiperidine and synthetic method, which is applied in the field of synthesis, and can solve problems such as few literature reports
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Embodiment 1
[0019] Example 1: Synthesis of tert-butyl 3-difluoromethyl-piperidine-1-carboxylate: add 2.13 g of 1-tert-butoxycarbonyl-3-piperidinecarbaldehyde (10 mmol, 1 eq) to a three-necked flask, and use 20 mL of anhydrous dichloromethane was dissolved and stirred at -5°C in a low temperature cooling bath. Dissolve 4.84g of DAST reagent (30mmol, 3eq) in 100mL of anhydrous dichloromethane, and slowly add the resulting solution dropwise (to finish dropping in about 90min) into the reaction solution. The reaction was followed (PE:EA=10:1), and the reaction was terminated after about 18h. Then, a saturated sodium bicarbonate solution was slowly added dropwise (about 1 d / s) to the reaction system to remove the unreacted DAST reagent until no obvious bubbles were generated. The reaction solution was extracted with dichloromethane, and the aqueous layer was extracted three times with dichloromethane after separation. The organic layers were combined, washed with 5% sodium bicarbonate soluti...
Embodiment 2
[0021] Example 2: Synthesis of tert-butyl 3-difluoromethyl-piperidine-1-carboxylate: add 2.13 g of 1-tert-butoxycarbonyl-3-piperidinecarbaldehyde (10 mmol, 1 eq) to a three-necked flask, and use 20 mL of anhydrous dichloromethane was dissolved and stirred at -25°C in a low temperature cooling bath. 9.68g of DAST reagent (60mmol, 6eq) was dissolved in 100mL of anhydrous dichloromethane, and the resulting solution was slowly added dropwise (the drop was completed in about 90min) into the reaction solution, and after the drop was added, stirred at -25°C overnight, and spotted with TLC Follow up the reaction (PE:EA=10:1), the reaction is completed after about 25h, and then slowly dropwise (about 1d / s) saturated sodium bicarbonate solution into the reaction system to remove the unreacted DAST reagent until no obvious bubbles are generated. . The reaction solution was extracted with dichloromethane, and the aqueous layer was extracted three times with dichloromethane after separati...
Embodiment 3
[0023] Example 3: Synthesis of tert-butyl 3-difluoromethyl-piperidine-1-carboxylate: add 2.13 g of 1-tert-butoxycarbonyl-3-piperidinecarbaldehyde (10 mmol, 1 eq) to a three-necked flask, and use 20 mL of anhydrous dichloromethane was dissolved and stirred at 15°C in a low temperature cooling bath. 8.07g of DAST reagent (50mmol, 5eq) was dissolved in 100mL of anhydrous dichloromethane, and the resulting solution was slowly added dropwise (about 90min) into the reaction solution, and after the dropwise addition was completed, stirred at 15°C overnight, followed by a TLC spot plate. Reaction (PE:EA=10:1), the reaction is carried out for about 15h to complete the reaction, and then slowly dropwise (about 1d / s) saturated sodium bicarbonate solution is added to the reaction system to remove the unreacted DAST reagent until no obvious bubbles are generated. The reaction solution was extracted with dichloromethane, and the aqueous layer was extracted three times with dichloromethane a...
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