Tetrahydrofuran → Tert-butyl 4-(2-([1,2,4]triazolo[4,3-a]pyridin-3-yl)-6-fluoroquinolin-8-yloxy)-3,3-difluoropiperidine-1-carboxylate

HRID 876475Notes

Reaction equation

HRID 876475 reaction equation
[F:1][C:2]1([F:16])[CH:7]([OH:8])[CH2:6][CH2:5][N:4]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:3]1.CC([O-])(C)C.[K+].C1COCC1.[N:28]1[N:29]=[C:30]([C:37]2[CH:46]=[CH:45][C:44]3[C:39](=[C:40](F)[CH:41]=[C:42]([F:47])[CH:43]=3)[N:38]=2)[N:31]2[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=12>CN(C=O)C>[N:28]1[N:29]=[C:30]([C:37]2[CH:46]=[CH:45][C:44]3[C:39](=[C:40]([O:8][CH:7]4[CH2:6][CH2:5][N:4]([C:9]([O:11][C:12]([CH3:13])([CH3:15])[CH3:14])=[O:10])[CH2:3][C:2]4([F:1])[F:16])[CH:41]=[C:42]([F:47])[CH:43]=3)[N:38]=2)[N:31]2[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=12

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 23665647Potassium tert-butoxideHCID 56932106tert-Butyl 3,3-difluoro-4-hydroxypiperidine-1-carboxylateHCID 672304752-([1,2,4]Triazolo[4,3-a]pyridin-3-yl)-6,8-difluoroquinoline

Product 1

HCID 67234219Tert-butyl 4-(2-([1,2,4]triazolo[4,3-a]pyridin-3-yl)-6-fluoroquinolin-8-yloxy)-3,3-difluoropiperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

tert-Butyl 3,3-difluoro-4-hydroxypiperidine-1-carboxylate (0.0706 g, 0.298 mmol) was treated with 1 M KOtBu in THF (0.283 mL, 0.283 mmol) and stirred for 15 minutes. The solution was treated with 2-([1,2,4]triazolo[4,3-a]pyridin-3-yl)-6,8-difluoroquinoline (0.042 g, 0.149 mmol) and DMF (0.80 mL) then the mixture was stirred at ambient temperature for 16 hours. The mixture was directly chromatographed on SiO2 eluting with a gradient of 2% NH4OH in isopropanol/ethyl acetate. The desired product was collected and concentrated to a colorless oil, (72 mg). MS APCI (+) m/z 500.0 (M+1) detected.

Workup

  1. stirringthe mixture was stirred at ambient temperature for 16 hours
  2. customThe mixture was directly chromatographed on SiO2 eluting with a gradient of 2% NH4OH in isopropanol/ethyl acetate
  3. customThe desired product was collected
  4. concentrationconcentrated to a colorless oil, (72 mg)

Sources & evidence

ORD record
ord-2535f08836c74f35ba1f10b05f99e767
Source dataset
uspto-grants-2015_03
Patent number
US08987251B2

Reaction notes

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