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

HRID 402431Notes

Reaction equation

HRID 402431 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]([CH2:13][OH:14])=[C:11]([CH3:15])[N:10]=[N:9]2)=[CH:4][CH:3]=1.[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>[CH3:26][O:25][C:23](=[O:24])[C:22]1[CH:27]=[CH:28][C:19]([O:14][CH2:13][C:12]2[N:8]([C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=3)[N:9]=[N:10][C:11]=2[CH3:15])=[N:20][CH:21]=1

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 254249Methyl 6-chloropyridine-3-carboxylateHCID 19914681(1-(4-Fluorophenyl)-4-methyl-1H-1,2,3-triazol-5-yl)methanol

Product 1

HCID 573354046-[3-(4-fluoro-phenyl)-5-methyl-3H-[1,2,3]triazol-4-ylmethoxy]-nicotinic acid methyl esterYield 88.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

A solution of [3-(4-fluoro-phenyl)-5-methyl-3H-[1,2,3]triazol-4-yl]-methanol (425 mg, 2.05 mmol) in THF (3 mL) was added dropwise at 0° C. to a suspension of NaH (55% in oil, 100 mg, 2.05 mmol) in THF (6 mL) and the reaction mixture was then stirred at room temperature for 30 min. Then a solution of methyl 6-chloronicotinate (390 mg, 8.0 mmol) in THF (3 mL) was added dropwise at 0° C. and the reaction mixture stirred at room temperature for 20 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, 10 to 50% ethyl acetate in heptane) afforded the title compound (621 mg, 88%) as a white solid. MS: m/e=343.3 [M+H]+.

Workup

  1. stirringthe reaction mixture stirred at room temperature for 20 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, 10 to 50% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-43b11e09e8a14b6c8ce158e1012f5d9d
Source dataset
uspto-grants-2014_06
Patent number
US08742097B2

Reaction notes

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