Water → ethyl 1-(2-fluorobenzyl)-5-(thiazol-2-yl)-1H-1,2,4-triazole-3-carboxylate

HRID 2174288Notes

Reaction equation

HRID 2174288 reaction equation
[S:1]1[CH:5]=[CH:4][N:3]=[C:2]1[C:6]1[N:10]=[C:9]([C:11]([O:13][CH2:14][CH3:15])=[O:12])[NH:8][N:7]=1.[H-].[Na+].Br[CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=1[F:26].O>CN(C=O)C>[F:26][C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=1[CH2:19][N:7]1[C:6]([C:2]2[S:1][CH:5]=[CH:4][N:3]=2)=[N:10][C:9]([C:11]([O:13][CH2:14][CH3:15])=[O:12])=[N:8]1.[F:26][C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=1[CH2:19][N:8]1[C:9]([C:11]([O:13][CH2:14][CH3:15])=[O:12])=[N:10][C:6]([C:2]2[S:1][CH:5]=[CH:4][N:3]=2)=[N:7]1

Participants

7

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 67968alpha-Bromo-o-fluorotolueneHCID 178470224HCID 178470224, compound

Product 2

HCID 69093312ethyl 1-(2-fluorobenzyl)-5-(thiazol-2-yl)-1H-1,2,4-triazole-3-carboxylateYield 48%HCID 69094030ethyl 1-(2-fluorobenzyl)-3-(thiazol-2-yl)-1H-1,2,4-triazole-5-carboxylateYield 44%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of ethyl 3-(thiazol-2-yl)-1H-1,2,4-triazole-5-carboxylate (Intermediate-2, 1.7 mmol) in DMF (8 mL) was added sodium hydride (1.2 equiv). After 10 min, 1-(bromomethyl)-2-fluorobenzene (1.2 equiv) was added. The reaction was stirred at ambient temperature for 35 min. The reaction mixture was poured into water and extracted with EtOAc. The organic phases were washed with water and brine, dried over Na2SO4, filtered and conc. The crude product was purified using SiO2 chromatography and an appropriate solvent gradient (EtOAc/hexanes) to give ethyl 1-(2-fluorobenzyl)-5-(thiazol-2-yl)-1H-1,2,4-triazole-3-carboxylate (48%) and ethyl 1-(2-fluorobenzyl)-3-(thiazol-2-yl)-1H-1,2,4-triazole-5-carboxylate as white solids (44% yield).

Workup

  1. extractionextracted with EtOAc
  2. washThe organic phases were washed with water and brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. customconc. The crude product was purified

Sources & evidence

ORD record
ord-42b9f11f066d4ce098729872d3a3bad8
Source dataset
uspto-grants-2015_06
Patent number
US09061030B2

Reaction notes

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