Water → Ethyl 1-(2-fluorophenyl)-5-(tetrahydro-2H-pyran-4-yl)-1H-1,2,3-triazole-4-carboxylate

HRID 219568Notes

Reaction equation

HRID 219568 reaction equation
C1CCN2C(=NCCC2)CC1.[CH2:12]([O:14][C:15](=[O:25])[CH2:16][C:17](=O)[CH:18]1[CH2:23][CH2:22][O:21][CH2:20][CH2:19]1)[CH3:13].[N:26]([C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=1[F:35])=[N+:27]=[N-:28].O>CN(C=O)C>[F:35][C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][C:29]=1[N:26]1[C:17]([CH:18]2[CH2:23][CH2:22][O:21][CH2:20][CH2:19]2)=[C:16]([C:15]([O:14][CH2:12][CH3:13])=[O:25])[N:28]=[N:27]1

Participants

6

Reactant 4

HCID 962WaterHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 116079241-Azido-2-fluorobenzeneHCID 23144053Ethyl 3-(oxan-4-yl)-3-oxopropanoate

Product 1

HCID 68648996Ethyl 1-(2-fluorophenyl)-5-(tetrahydro-2H-pyran-4-yl)-1H-1,2,3-triazole-4-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

DBU (1.32 ml; 8.82 mmol; 1.10 eq.) was dissolved in DMF (16.5 ml) and put under nitrogen atmosphere. 3-Oxo-3-(tetrahydro-pyran-4-yl)-propionic acid ethyl ester (Pharmacore, 1.767 g; 8.82 mmol; 1.10 eq.) was added to the mixture and it was stirred for 15 min. Then a solution of 1-azido-2-fluorobenzene, prepared according to Platz, M. S. et al. J. Org. Chem. 1989, 54, 5938-5945, (1.1 g; 8.02 mmol; 1 eq.) in DMF (15 mL) was added dropwise to the solution at room temperature. The reaction mixture was stirred at 70° C. for 2 hours. Water (40 mL) was added to the reaction mixture. The aqueous layer was extracted with EtOAc (3×40 mL). Combined organic layers were washed with HCl 0.1N, brine, dried over MgSO4 and concentrated under vacuum giving the title compound as a yellow oil. It was used in the next step without further purification. LC/MS (Method B): 320.2 (M+H)+.

Workup

  1. stirringThe reaction mixture was stirred at 70° C. for 2 hours
  2. extractionThe aqueous layer was extracted with EtOAc (3×40 mL)
  3. washCombined organic layers were washed with HCl 0.1N, brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-dbcf062b0b8744c8aed5f5d246ac469f
Source dataset
uspto-grants-2012_06
Patent number
US08202856B2

Reaction notes

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