Reaktion #86745

Reaktionsgleichung

4-(3-fluoro-2-trifluoromethyl)phenylpiperidine hydrochloride

4-(3-Fluoro-2-(trifluoromethyl)phenyl)piperidine Hydrochloride

benzotriazole-1-yl-oxy-tris-(dimethylamino)-phosphonium hexafluorophosphate

diisopropylethylamine

ethyl 6-bromo-[1,2,4]triazolo[4,3-a]pyridine-3-carboxylate

LiOH.H2O

HCl

→

(6-bromo-[1,2,4]triazolo[4,3-a]pyridin-3-yl)(4-(3-fluoro-2-(trifluoromethyl)phenyl)piperidin-1-yl)methanone

Lösungsmittel

H2O

THF

H2O

Reaktionsbedingungen

Aufarbeitung

1. 1
   EinengenThe mixture was concentrated under reduced pressure
2. 2
   workup.ADDITIONThe obtained residue was diluted in DMF (3.0 mL) under an atmosphere of N2
3. 3
   workup.STIRRINGThe mixture was stirred at ambient temperature for 18 h
4. 4
   ExtraktionThe mixture was extracted with EtOAc (4×30 mL)
5. 5
   WaschenThe combined organic layers were washed with 5% lithium chloride solution (4×20 mL)
6. 6
   Einengenconcentrated under reduced pressure
7. 7
   SonstigeThe resulting residue was chromatographed over silica gel (Isco CombiFlash Rf unit, 12 g Redisep column, 0% to 50% EtOAc in hexanes)

Vorschrift

To a solution of ethyl 6-bromo-[1,2,4]triazolo[4,3-a]pyridine-3-carboxylate (75 mg, 0.28 mmol) in THF (2.3 mL) was added a solution of LiOH.H2O (23 mg, 0.56 mmol) in H2O (1.5 mL). The mixture was stirred for 20 min and was neutralized with 2N HCl. The mixture was concentrated under reduced pressure. The obtained residue was diluted in DMF (3.0 mL) under an atmosphere of N2. To this mixture was added 4-(3-fluoro-2-trifluoromethyl)phenylpiperidine hydrochloride (5, 78 mg, 0.28 mmol), benzotriazole-1-yl-oxy-tris-(dimethylamino)-phosphonium hexafluorophosphate (245 mg, 0.556 mmol), and diisopropylethylamine (107 mg, 0.834 mmol). The mixture was stirred at ambient temperature for 18 h. The resulting mixture was diluted with H2O (20 mL). The mixture was extracted with EtOAc (4×30 mL). The combined organic layers were washed with 5% lithium chloride solution (4×20 mL) and concentrated under reduced pressure. The resulting residue was chromatographed over silica gel (Isco CombiFlash Rf unit, 12 g Redisep column, 0% to 50% EtOAc in hexanes) to provide (6-bromo-[1,2,4]triazolo[4,3-a]pyridin-3-yl)(4-(3-fluoro-2-(trifluoromethyl)phenyl)piperidin-1-yl)methanone as an orange film (87 mg, 66%): 1H NMR (300 MHz, DMSO-d6) δ 9.13-9.10 (m, 1H), 7.75-7.62 (m, 2H), 7.52-7.46 (m, 1H), 7.38-7.25 (m, 1H), 5.30-5.17 (m, 1H), 4.78-4.64 (m, 1H), 3.42-3.28 (m, 3H, overlaps with H2O), 3.11-2.92 (m, 1H), 1.98-1.70 (m, 4H); ESI MS m/z 471 [M+H]+.

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