Hydrochloric Acid → 5-Chloro-4-cyclopropylmethoxy-pyridine-2-carboxylic acid

HRID 1480040

Reaction equation

HRID 1480040 reaction equation
[Cl:1][C:2]1[C:3](I)=[CH:4][C:5]([C:8]([OH:10])=[O:9])=[N:6][CH:7]=1.CC(C)([O-])C.[K+].[CH:18]1([CH2:21][OH:22])[CH2:20][CH2:19]1.Cl>C1COCC1.CN(C=O)C>[Cl:1][C:2]1[C:3]([O:22][CH2:21][CH:18]2[CH2:20][CH2:19]2)=[CH:4][C:5]([C:8]([OH:10])=[O:9])=[N:6][CH:7]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 75644CyclopropanemethanolHCID 23665647Potassium tert-butoxideHCID 855920915-Chloro-4-iodo-2-pyridinecarboxylic acid

Product 1

HCID 902036385-Chloro-4-cyclopropylmethoxy-pyridine-2-carboxylic acidYield 57.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 5-chloro-4-iodo-pyridine-2-carboxylic acid (CAN 120643-06-3, 600 mg, 2.12 mmol) in THF (20 mL) and DMF (2 mL) was added with stirring potassium tert-butoxide (1.0 g, 8.91 mmol) and cyclopropanemethanol (1.5 mL, 18.8 mmol). The resulting mixture was stirred at 80° C. for 25 h, cooled, acidified with hydrochloric acid (25 mL, 1 N) and partitioned into ethyl acetate. The organic portions were combined, dried over Na2SO4, filtered and concentrated. The residue was purified by prep. HPLC (Gemini NX, acetonitrile/water gradient) to give the title compound (276 mg, 57%) as light yellow solid. MS (ESI, m/z): 228.4 (MH+).

Workup

  1. temperaturecooled
  2. custompartitioned into ethyl acetate
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by prep

Sources & evidence

ORD record
ord-facf010612ba417b850001705fe85ca0
Source dataset
uspto-grants-2016_08
Patent number
US09409866B2

Linked notes

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