Water → 6-(3-methyl-5-pyridin-2-yl-3H-[1,2,3]triazol-4-ylmethoxy)-nicotinic acid methyl ester

HRID 402376Notes

Reaction equation

HRID 402376 reaction equation
[CH3:1][N:2]1[C:6]([CH2:7][OH:8])=[C:5]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][N:10]=2)[N:4]=[N:3]1.[H-].[Na+].Cl[C:18]1[CH:27]=[CH:26][C:21]([C:22]([O:24][CH3:25])=[O:23])=[CH:20][N:19]=1.O>C1COCC1>[CH3:25][O:24][C:22](=[O:23])[C:21]1[CH:26]=[CH:27][C:18]([O:8][CH2:7][C:6]2[N:2]([CH3:1])[N:3]=[N:4][C:5]=2[C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][N:10]=2)=[N:19][CH:20]=1

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 254249Methyl 6-chloropyridine-3-carboxylateHCID 67498007(3-methyl-5-pyridin-2-yl-3H-[1,2,3]triazol-4-yl)-methanol

Product 1

HCID 573346466-(3-methyl-5-pyridin-2-yl-3H-[1,2,3]triazol-4-ylmethoxy)-nicotinic acid methyl esterYield 77.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

A solution of (3-methyl-5-pyridin-2-yl-3H-[1,2,3]triazol-4-yl)-methanol (158 mg, 0.83 mmol) in THF (2.4 mL) was added dropwise at 0° C. to a suspension of NaH (60% in oil, 40 mg, 0.91 mmol) in THF (1.2 mL) and the reaction mixture was then stirred at room temperature for 30 min. Then a solution of methyl 6-chloronicotinate (157 mg, 0.91 mmol) in THF (2.4 mL) was added dropwise at 0° C. and the reaction mixture stirred at room temperature for 18 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 (209 mg, 77%) as a white solid. MS: m/e=326.1 [M+H]+.

Workup

  1. stirringthe reaction mixture stirred at room temperature for 18 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-f32c7938bfb3444dba4ea9f0deabd39f
Source dataset
uspto-grants-2014_06
Patent number
US08742097B2

Reaction notes

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