Hydrochloric Acid → Methyl 6-butoxypyridine-2-carboxylate

HRID 912698Notes

Reaction equation

HRID 912698 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]([O:10][CH3:11])=[O:9])[CH:5]=[CH:4][CH:3]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+].Cl.[CH2:23]([O:27]C1N=C(C(O)=O)C=CC=1)[CH2:24][CH2:25][CH3:26].S(Cl)(Cl)=O>C(O)CCC>[CH2:23]([O:27][C:2]1[N:7]=[C:6]([C:8]([O:10][CH3:11])=[O:9])[CH:5]=[CH:4][CH:3]=1)[CH2:24][CH2:25][CH3:26]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 24386Thionyl ChlorideHCID 242723Methyl 6-chloropicolinateHCID 2724254Sodium bis(trimethylsilyl)amide2×HCID 132095466-Butoxypicolinic acid

Product 1

HCID 67415067Methyl 6-butoxypyridine-2-carboxylateYield 78%

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Procedure

To methyl 6-chloro-pyridine-2-carboxylate (2.58 g, 15.0 mmol, obtained from Example 17(a)) was added 1-butanol (35 mL) followed by sodium bis(trimethylsilyl)amide (5.51 g, 30.1 mmol). The suspension was warmed to 130° C. for 24 h after which more sodium bis(trimethylsilyl)amide (5.51 g, 30.1 mmol) was added. After another 24 h at reflux, the solution was cooled to r.t. and was poured into 200 mL 1N HCl in an ice bath. The aqueous solution was extracted twice with ethyl acetate. The organic layers were combined, dried over sodium sulfate, filtered and concentrated in vacuo resulting in 3.79 g of crude 6-butoxy-pyridine-2-carboxylic acid. To the crude 6-butoxy-pyridine-2-carboxylic acid was added thionyl chloride (100 mL) and after 1 h the resulting solution was concentrated in vacuo. To the residue was slowly added anhydrous methanol (100 mL) and after stirring o.n., the solvents were removed in vacuo. The resulting 3.73 g of crude material was purified by silica gel column chromatography (hexanes/ethyl acetate, 8:1) resulting in 2.46 g of the title compound as a colourless oil (78% yield, 11.7 mmol).

Workup

  1. additionwas added
  2. temperatureAfter another 24 h at reflux
  3. extractionThe aqueous solution was extracted twice with ethyl acetate
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customresulting in 3.79 g of crude 6-butoxy-pyridine-2-carboxylic acid
  8. concentrationafter 1 h the resulting solution was concentrated in vacuo
  9. custom, the solvents were removed in vacuo
  10. customThe resulting 3.73 g of crude material was purified by silica gel column chromatography (hexanes/ethyl acetate, 8:1)

Sources & evidence

ORD record
ord-a4936bcac3ae4839a7a3f2bd2f4b20dc
Source dataset
uspto-grants-2011_09
Patent number
US08026244B2

Reaction notes

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