Potassium Phosphate, Tribasic → 5-Cyclopropyl-6-cyclopropylmethoxy-pyridine-2-carboxylic acid

HRID 624843

Reaction equation

HRID 624843 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([C:13]([OH:15])=[O:14])=[N:6][C:7]=1[O:8][CH2:9][CH:10]1[CH2:12][CH2:11]1.[CH:16]1(B(O)O)[CH2:18][CH2:17]1.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C1(C)C=CC=CC=1.O.C([O-])(=O)C.C([O-])(=O)C.[Pd+2]>[CH:16]1([C:2]2[CH:3]=[CH:4][C:5]([C:13]([OH:15])=[O:14])=[N:6][C:7]=2[O:8][CH2:9][CH:10]2[CH2:12][CH2:11]2)[CH2:18][CH2:17]1

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 2760897Cyclopropylboronic acidHCID 710875435-Bromo-6-cyclopropylmethoxy-pyridine-2-carboxylic acid

Product 1

HCID 710873465-Cyclopropyl-6-cyclopropylmethoxy-pyridine-2-carboxylic acidYield 75%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 22272177Toluene waterSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 5-bromo-6-(cyclopropylmethoxy)-pyridine-2-carboxylic acid (1.5 g, 5.5 mmol), cyclopropylboronic acid (CAN 411235-57-9, 0.57 g, 7 mmol), palladium diacetate (CAN 3375-31-3, 62 mg, 0.28 mmol), tricyclohexylphosphine (CAN 2622-14-2, 154 mg, 0.1 mmol) and potassium phosphate (4.1 g, 19 mmol) in toluene/water (20/1 v/v, 30 mL) was heated to 100° C. overnight. After that the mixture was evaporated to dryness, dissolved in 30 mL of water, extracted with ethyl acetate (30 mL) and the organic layer was dropped. The water layer was adjusted to pH=3 and extracted with ethyl acetate (2×30 mL), this organic layer was washed with water (30 mL) and brine (30 mL), dried over anhydrous sodium sulfate then evaporated to dryness. The residue was purified by column chromatography (silica gel, 10 g, eluting with 15% ethyl acetate in petroleum ether) to obtain the title compound (0.96 g, 75%) as white solid; MS (LC/MS): 234.1 [MH+].

Workup

  1. customAfter that the mixture was evaporated to dryness
  2. dissolutiondissolved in 30 mL of water
  3. extractionextracted with ethyl acetate (30 mL)
  4. additionthe organic layer was dropped
  5. extractionextracted with ethyl acetate (2×30 mL)
  6. washthis organic layer was washed with water (30 mL) and brine (30 mL)
  7. dry with materialdried over anhydrous sodium sulfate
  8. customthen evaporated to dryness
  9. customThe residue was purified by column chromatography (silica gel, 10 g, eluting with 15% ethyl acetate in petroleum ether)

Sources & evidence

ORD record
ord-ea8df08f6c5c487a9a321ba139eb2068
Source dataset
uspto-grants-2016_04
Patent number
US09303012B2

Linked notes

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