Sodium hydride → Ethyl 8-[(4-chlorophenoxy)methyl]-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 71177

Reaction equation

HRID 71177 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:15]2[N:19]3[CH2:20][CH2:21][CH2:22][CH:23]([C:24]([O:26][CH2:27][CH3:28])=[O:25])[C:18]3=[N:17][N:16]=2)[CH:6]=[CH:7][C:8]=1[C:9]1[O:13][C:12]([CH3:14])=[N:11][CH:10]=1.[H-].[Na+].[Cl:31][C:32]1[CH:37]=[CH:36][C:35]([O:38][CH2:39]Cl)=[CH:34][CH:33]=1.[Cl-].[NH4+]>CN(C=O)C>[Cl:31][C:32]1[CH:37]=[CH:36][C:35]([O:38][CH2:39][C:23]2([C:24]([O:26][CH2:27][CH3:28])=[O:25])[CH2:22][CH2:21][CH2:20][N:19]3[C:15]([C:5]4[CH:6]=[CH:7][C:8]([C:9]5[O:13][C:12]([CH3:14])=[N:11][CH:10]=5)=[C:3]([O:2][CH3:1])[CH:4]=4)=[N:16][N:17]=[C:18]23)=[CH:34][CH:33]=1

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 88801alpha,4-DichloroanisoleHCID 66608236Ethyl 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

Product 1

HCID 66608313Ethyl 8-[(4-chlorophenoxy)methyl]-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 32.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

Under ice-cooling and an argon stream, to a mixture of ethyl 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 (1000 mg) in DMF (15 mL) was added sodium hydride (60%, 115 mg), and the mixture was stirred at 0° C. for 30 min. 1-Chloro-4-(chloromethoxy)benzene (694 mg) was added, and the mixture was stirred at 0° C. for 1 hr. Saturated aqueous ammonium chloride was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with saturated aqueous sodium hydrogen carbonate solution and 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 (440 mg).

Workup

  1. temperatureUnder ice-cooling
  2. stirringthe mixture was stirred at 0° C. for 1 hr
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe extract was washed with saturated aqueous sodium hydrogen carbonate solution and 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-bc044d32620040e5ba889697abd459b4
Source dataset
uspto-grants-2014_09
Patent number
US08822699B2

Linked notes

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