Sodium ethoxide → Ethyl 8-[6-(2-ethoxy-2-oxoethyl)-2,3,4-trifluorophenoxy]-3-[3-methoxy-4-(2-methyl-1,3-oxazol-5-yl)phenyl]-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridine-8-carboxylate

HRID 71219Notes

Reaction equation

HRID 71219 reaction equation
[F:1][C:2]1[C:3]([OH:16])=[C:4]([CH2:10][C:11]([O:13][CH2:14][CH3:15])=[O:12])[CH:5]=[C:6]([F:9])[C:7]=1[F:8].[O-]CC.[Na+].Cl[C:22]1([C:45]([O:47][CH2:48][CH3:49])=[O:46])[CH2:27][CH2:26][CH2:25][N:24]2[C:28]([C:31]3[CH:36]=[CH:35][C:34]([C:37]4[O:41][C:40]([CH3:42])=[N:39][CH:38]=4)=[C:33]([O:43][CH3:44])[CH:32]=3)=[N:29][N:30]=[C:23]12>C(O)C.[Cl-].[NH4+]>[CH2:14]([O:13][C:11](=[O:12])[CH2:10][C:4]1[C:3]([O:16][C:22]2([C:45]([O:47][CH2:48][CH3:49])=[O:46])[CH2:27][CH2:26][CH2:25][N:24]3[C:28]([C:31]4[CH:36]=[CH:35][C:34]([C:37]5[O:41][C:40]([CH3:42])=[N:39][CH:38]=5)=[C:33]([O:43][CH3:44])[CH:32]=4)=[N:29][N:30]=[C:23]23)=[C:2]([F:1])[C:7]([F:8])=[C:6]([F:9])[CH:5]=1)[CH3:15]

Participants

6

Reactant 3

HCID 2723922Sodium ethoxideHCID 66604255Ethyl 8-chloro-3-[3-methoxy-4-(2-methyl-1,3-oxazol-5-yl)phenyl]-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridine-8-carboxylateHCID 86662985Ethyl (3,4,5-trifluoro-2-hydroxyphenyl)acetate

Product 1

HCID 86662984Ethyl 8-[6-(2-ethoxy-2-oxoethyl)-2,3,4-trifluorophenoxy]-3-[3-methoxy-4-(2-methyl-1,3-oxazol-5-yl)phenyl]-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridine-8-carboxylateYield 45.2%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 25517Ammonium ChlorideSolvent

Procedure

To a mixture of ethyl (3,4,5-trifluoro-2-hydroxyphenyl)acetate (1.77 g) in ethanol (15 mL) was added sodium ethoxide (0.514 g) at room temperature under a nitrogen atmosphere, and the mixture was stirred for 30 min. To the reaction mixture was added ethyl 8-chloro-3-[3-methoxy-4-(2-methyl-1,3-oxazol-5-yl)phenyl]-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridine-8-carboxylate (3 g), the mixture was stirred at 80° C. overnight under a nitrogen atmosphere, and diluted with saturated aqueous ammonium chloride solution, and the mixture was extracted with ethyl acetate. The organic layer was separated, washed with saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (2 g).

Workup

  1. stirringthe mixture was stirred at 80° C. overnight under a nitrogen atmosphere
  2. extractionthe mixture was extracted with ethyl acetate
  3. customThe organic layer was separated
  4. washwashed with saturated brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customthe solvent was evaporated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography (ethyl acetate/hexane)

Sources & evidence

ORD record
ord-f7ace9d6d83745d0b79cecce5abb0416
Source dataset
uspto-grants-2014_09
Patent number
US08822699B2

Reaction notes

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