Water → Methyl 6-((4-(2-fluorophenyl)-1-methyl-1H-1,2,3-triazol-5-yl)methoxy)nicotinate

HRID 402366Notes

Reaction equation

HRID 402366 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[N:9]=[N:10][N:11]([CH3:15])[C:12]=1[CH2:13][OH:14].[H-].[Na+].Cl[C:19]1[CH:28]=[CH:27][C:22]([C:23]([O:25][CH3:26])=[O:24])=[CH:21][N:20]=1.O>C1COCC1>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[N:9]=[N:10][N:11]([CH3:15])[C:12]=1[CH2:13][O:14][C:19]1[CH:28]=[CH:27][C:22]([C:23]([O:25][CH3:26])=[O:24])=[CH:21][N:20]=1

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 254249Methyl 6-chloropyridine-3-carboxylateHCID 67498210(4-(2-Fluorophenyl)-1-methyl-1H-1,2,3-triazol-5-yl)methanol

Product 1

HCID 57334494Methyl 6-((4-(2-fluorophenyl)-1-methyl-1H-1,2,3-triazol-5-yl)methoxy)nicotinateYield 67%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

A solution of (4-(2-fluorophenyl)-1-methyl-1H-1,2,3-triazol-5-yl)methanol (100 mg, 0.48 mmol) in THF (1.4 mL) was added dropwise at 0° C. to a suspension of NaH (60% in oil, 21 mg, 0.53 mmol) in THF (0.7 mL) and the reaction mixture was then stirred at room temperature for 30 min. Then a solution of methyl 6-chloronicotinate (91 mg, 0.53 mmol) in THF (1 mL) was added dropwise at 0° C. and the reaction mixture stirred at room temperature for 16 h. The mixture was then poured into water extracted with ethyl acetate and the combined organic extracts washed with brine, dried over sodium sulphate, filtered and evaporated. Purification by chromatography (silica, 0 to 100% ethyl acetate in heptane) afforded the title compound (110 mg, 67%) as a colourless gum. MS: m/e=343.1 [M+H]+.

Workup

  1. stirringthe reaction mixture stirred at room temperature for 16 h
  2. extractionextracted with ethyl acetate
  3. washthe combined organic extracts washed with brine
  4. dry with materialdried over sodium sulphate
  5. filtrationfiltered
  6. customevaporated
  7. customPurification by chromatography (silica, 0 to 100% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-8c1cac9016774b5ab46638452efde75b
Source dataset
uspto-grants-2014_06
Patent number
US08742097B2

Reaction notes

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