Boron trifluoride etherate → HCID 67492215, compound

HRID 1921373Notes

Reaction equation

HRID 1921373 reaction equation
[CH2:1]([C:3]1[C:4]([O:14][CH3:15])=[N:5][C:6]([CH3:13])=[C:7]([CH:12]=1)[C:8]([NH:10][OH:11])=[NH:9])[CH3:2].[CH2:16](OC(OCC)OCC)C.B(F)(F)F.CCOCC>>[CH2:1]([C:3]1[C:4]([O:14][CH3:15])=[N:5][C:6]([CH3:13])=[C:7]([C:8]2[N:9]=[CH:16][O:11][N:10]=2)[CH:12]=1)[CH3:2]

Participants

4

Reactant 3

HCID 8000Boron trifluoride etherateHCID 31214Ethyl orthoformateHCID 178436635HCID 178436635, compound

Product 1

HCID 67492215HCID 67492215, compoundYield 15%

Conditions

Temperature
100 °C

Procedure

To a crude mixture of 5-ethyl-N-hydroxy-6-methoxy-2-methylnicotinamidine (formed on 1.705 mmol scale following the procedures of Step 3, Example 22), under a nitrogen atmosphere, is added triethylorthoformate (2 mL), followed by boron trifluoride etherate (42.6 μL, 0.336 mmol). The resulting solution mixture is heated at 100° C. for 3.25 hr. The mixture is allowed to cool, concentrated under vacuum, then treated with aqueous hydrochloric acid (1M, 2 mL). The resulting mixture is allowed to stand for 30 min before making basic with excess solid sodium bicarbonate. The mixture is extracted with five portions of ethyl acetate, dried over magnesium sulfate, filtered and evaporated to leave an oily, brown residue that is purified by flash chromatography on a 5-gram silica gel cartridge by elution with heptane:dichloromethane (1:1, increasing to 4:1). Fractions containing the product are combined, the solvent evaporated and re-purified by flash chromatography on a 5-gram silica gel cartridge by elution with heptane:dichloromethane (9:1, increasing to 17:3 then 1:1). Fractions containing the product are combined, the solvent evaporated and further purified by flash chromatography on a 5-gram silica gel cartridge by elution with heptane:dichloromethane (87:13, then 1:1). Clean fractions containing the product are combined, evaporated and triturated with heptane to give 3-ethyl-2-methoxy-6-methyl-5-(1,2,4-oxadiazol-3-yl)-pyridine (57 mg, 15% yield, 2 steps). MS: m/e=220 (M+H); 1H NMR (300 MHz, CDCl3, δ, ppm): 8.72 (1H, s), 7.99 (1H, s), 4.00 (3H, s), 2.76 (3H, s), 2.61 (2H, q), 1.11 (3H, t)

Workup

  1. customformed on 1.705 mmol scale
  2. temperatureto cool
  3. concentrationconcentrated under vacuum
  4. additiontreated with aqueous hydrochloric acid (1M, 2 mL)
  5. extractionThe mixture is extracted with five portions of ethyl acetate
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. customevaporated
  9. customto leave an oily, brown residue that
  10. customis purified by flash chromatography on a 5-gram silica gel cartridge by elution with heptane:dichloromethane (1:1, increasing to 4:1)
  11. additionFractions containing the product
  12. customthe solvent evaporated
  13. customre-purified by flash chromatography on a 5-gram silica gel cartridge by elution with heptane:dichloromethane (9:1
  14. temperatureincreasing to 17:3
  15. additionFractions containing the product
  16. customthe solvent evaporated
  17. customfurther purified by flash chromatography on a 5-gram silica gel cartridge by elution with heptane:dichloromethane (87:13
  18. additionClean fractions containing the product
  19. customevaporated
  20. customtriturated with heptane

Sources & evidence

ORD record
ord-524bc8672c9f4af38d95283cccba45a5
Source dataset
uspto-grants-2012_05
Patent number
US08173682B2

Reaction notes

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