反应详情

Tert-butyl 4-(4-chloro-3-fluorophenyl)-4-cyanopiperidine-1-carboxylate (1.96 g, 5.785 mmol) was dissolved in concentrated HCl (48.21 mL, 578.5 mmol), heated to reflux, and then stirred over the weekend (approximately 60 hours). The reaction mixture was cooled to room temperature, transferred to a separatory funnel, and washed with ether. The aqueous layer was concentrated on a rotary evaporator and dried on a high vacuum line. The resulting solids were dissolved in 10% NaOH (9.255 g, 23.14 mmol), dioxane (40 mL) was added, followed by a Boc2O addition (1.326 g, 6.074 mmol). The reaction mixture was stirred at room temperature overnight (16 hours). The reaction mixture was then diluted with H2O and washed with ether. The aqueous layer was acidified with solid KHSO4, and then extracted with DCM. The combined extracts were dried (Na2SO4), filtered, concentrated and dried on a high vacuum line to give 1-(tert-butoxycarbonyl)-4-(4-chloro-3-fluorophenyl)piperidine-4-carboxylic acid (0.910 g, 43.96% yield) as a foam. LC/MS (APCI−) m/z 713 [2M−H]−.

1. temperatureheated
2. temperatureto reflux
3. customtransferred to a separatory funnel
4. washwashed with ether
5. concentrationThe aqueous layer was concentrated on a rotary evaporator
6. customdried on a high vacuum line
7. stirringThe reaction mixture was stirred at room temperature overnight (16 hours)
8. washwashed with ether
9. extractionextracted with DCM
10. dry with materialThe combined extracts were dried (Na2SO4)
11. filtrationfiltered
12. concentrationconcentrated
13. customdried on a high vacuum line