Sodium Bicarbonate → 3-Tert-butyl-7-[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridine

HRID 2047645Notes

Reaction equation

HRID 2047645 reaction equation
CC(C)([O-])C.[K+].[C:7]([C:11]1[N:15]2[CH2:16][CH2:17][CH:18]([C:20]([O:22]CC)=O)[CH2:19][C:14]2=[N:13][N:12]=1)([CH3:10])([CH3:9])[CH3:8].[F:25][C:26]1[CH:35]=[CH:34][C:29]([C:30](=[N:32]O)[NH2:31])=[CH:28][CH:27]=1.C(=O)(O)[O-].[Na+]>O1CCCC1.[Cl-].[Na+].O>[C:7]([C:11]1[N:15]2[CH2:16][CH2:17][CH:18]([C:20]3[O:22][N:32]=[C:30]([C:29]4[CH:34]=[CH:35][C:26]([F:25])=[CH:27][CH:28]=4)[N:31]=3)[CH2:19][C:14]2=[N:13][N:12]=1)([CH3:8])([CH3:9])[CH3:10]

Participants

7

Reactant 4

HCID 516892Sodium BicarbonateHCID 5930004-Fluoro-n-hydroxybenzimidamideHCID 23665647Potassium tert-butoxideHCID 67300535Ethyl 3-t-butyl-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridine-7-carboxylate

Product 1

HCID 673002453-Tert-butyl-7-[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridineYield 53.4%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 57417360Sodium chloride; waterSolvent

Procedure

Add dropwise potassium tert-butoxide 1M in tetrahydrofuran (2.08 Kg, 2.08 mol) to a solution of ethyl 3-tert-butyl-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridine-7-carboxylate (455 g, 1.81 mol) and 4-fluorobenzamidoxime (320 g, 2.08 mol) in tetrahydrofuran (11 L) at room temperature. Stir the reaction mixture for 16 hours. Pour the mixture over a solution of saturated sodium bicarbonate (6 L) and add brine (3×2 L). Separate phases and extract aqueous phase with ethyl acetate (3×1 L). Combine organics, dry over magnesium sulfate, filter, and concentrate to dryness under reduced pressure. Purify the resulting residue by silica gel chromatography eluting with ethyl acetate to ethyl acetate:methanol (9:1) to provide the title compound as a white solid (330 g). Mass spectrum (m/z): 342 (M+1).

Workup

  1. extractionSeparate phases and extract aqueous phase with ethyl acetate (3×1 L)
  2. dry with materialCombine organics, dry over magnesium sulfate
  3. filtrationfilter
  4. concentrationconcentrate to dryness under reduced pressure
  5. customPurify the resulting residue by silica gel chromatography
  6. washeluting with ethyl acetate to ethyl acetate:methanol (9:1)

Sources & evidence

ORD record
ord-48bc10895bab46198b3f8df157671d23
Source dataset
uspto-grants-2013_11
Patent number
US08592590B2

Reaction notes

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