2-Bromopropane → Methyl 5-isopropoxypicolinate

HRID 72942Notes

Reaction equation

HRID 72942 reaction equation
[OH:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]([O:10][CH3:11])=[O:9])=[N:6][CH:7]=1.C(=O)([O-])[O-].[K+].[K+].Br[CH:19]([CH3:21])[CH3:20]>CN(C=O)C>[CH:19]([O:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]([O:10][CH3:11])=[O:9])=[N:6][CH:7]=1)([CH3:21])[CH3:20]

Participants

5

Reactant 3

HCID 63582-BromopropaneHCID 11430Potassium CarbonateHCID 4715126Methyl 5-hydroxypyridine-2-carboxylate

Product 1

HCID 66610958Methyl 5-isopropoxypicolinateYield 73%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

To methyl 5-hydroxypyridine-2-carboxylate (0.6 g, 3.92 mmol) in DMF (3.6 mL) was added potassium carbonate (2.2 g, 15.7 mmol) followed by 2-bromopropane (736 μL, 7.8 mmol) The reaction mixture was heated at 60° C. for 1.5 hours. The reaction mixture was cooled and filtered using EtOAc and the solvent was evaporated under reduced pressure. The residue was dissolved in EtOAc and washed with water (3×10 mL) and brine solution (10 mL). The organics were separated and dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by silica gel column chromatography using 0-50% EtOAc: hexanes as eluent to give methyl 5-isopropoxypyridine-2-carboxylate (555 mg, 73%) as a colorless oil. ESI-MS m/z calc. 195.1. Found 196.3 (M+1)+; Retention time: 1.09 minutes (3 min run). Lithium hydroxide (5.7 mL of 2 M, 11.37 mmol) was added to a solution of methyl 5-isopropoxypyridine-2-carboxylate (555 mg, 2.84 mmol) in dioxane (4 mL) and stirred at 55° C. for 2 hours. The reaction mixture was diluted with ethyl acetate and washed with water and layers were separated. The aqueous layer was acidified with 1N HCl solution and extracted with ethyl acetate. The organics were separated and dried over sodium sulfate, filtered and concentrated in vacuo to give 5-isopropoxypyridine-2-carboxylic acid (150 mg, 29%). ESI-MS m/z calc. 182.1. Found 182.3 (M+1)+; Retention time: 0.33 minutes (3 min run).

Workup

  1. temperatureThe reaction mixture was cooled
  2. filtrationfiltered
  3. customthe solvent was evaporated under reduced pressure
  4. dissolutionThe residue was dissolved in EtOAc
  5. washwashed with water (3×10 mL) and brine solution (10 mL)
  6. customThe organics were separated
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-d32ab24eec2043fa859fa71ac7639832
Source dataset
uspto-grants-2014_09
Patent number
US08828996B2

Reaction notes

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