Tetrahydrofuran → (trans)-Benzyl 4-(2-([1,2,4]triazolo[4,3-a]pyridin-3-yl)quinolin-8-yloxy)-3-fluoropiperidine-1-carboxylate

HRID 876487Notes

Reaction equation

HRID 876487 reaction equation
[F:1][C@H:2]1[C@H:7]([OH:8])[CH2:6][CH2:5][N:4]([C:9]([O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[O:10])[CH2:3]1.CC([O-])(C)C.[K+].C1COCC1.[N:30]1[N:31]=[C:32]([C:39]2[CH:48]=[CH:47][C:46]3[C:41](=[C:42](F)[CH:43]=[CH:44][CH:45]=3)[N:40]=2)[N:33]2[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=12>CN(C=O)C>[N:30]1[N:31]=[C:32]([C:39]2[CH:48]=[CH:47][C:46]3[C:41](=[C:42]([O:8][C@@H:7]4[CH2:6][CH2:5][N:4]([C:9]([O:11][CH2:12][C:13]5[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=5)=[O:10])[CH2:3][C@H:2]4[F:1])[CH:43]=[CH:44][CH:45]=3)[N:40]=2)[N:33]2[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=12

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 23665647Potassium tert-butoxideHCID 52324488benzyl (3R,4R)-3-fluoro-4-hydroxypiperidine-1-carboxylateHCID 67232888HCID 67232888, compound

Product 1

HCID 131731020(trans)-Benzyl 4-(2-([1,2,4]triazolo[4,3-a]pyridin-3-yl)quinolin-8-yloxy)-3-fluoropiperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Non-racemic (trans)-benzyl 3-fluoro-4-hydroxypiperidine-1-carboxylate (0.192 g, 0.757 mmol) was treated with 1.0 M KOtBu in THF (0.757 mL, 0.757 mmol) and stirred at ambient temperature for 15 minutes. 2-([1,2,4]Triazolo[4,3-a]pyridin-3-yl)-8-fluoroquinoline (0.200 g, 0.757 mmol) was added along with DMF (2.25 mL) and the mixture was stirred at 50° C. for 15 hours. The reaction was cooled and chromatographed on SiO2, eluting with a gradient of 2% NH4OH in isopropanol/methylene chloride. After concentration in vacuo, the desired product was isolated as a beige solid (0.306 g). MS APCI (+) m/z 498.1 (M+1) detected.

Workup

  1. stirringthe mixture was stirred at 50° C. for 15 hours
  2. temperatureThe reaction was cooled
  3. customchromatographed on SiO2
  4. washeluting with a gradient of 2% NH4OH in isopropanol/methylene chloride
  5. concentrationAfter concentration in vacuo

Sources & evidence

ORD record
ord-09e133391a6d43949d575968f6f434af
Source dataset
uspto-grants-2015_03
Patent number
US08987251B2

Reaction notes

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