Cesium carbonate → 5-Cyclopropyl-6-(tetrahydro-furan-2-ylmethoxy)-pyridine-2-carboxylic acid

HRID 632226

Reaction equation

HRID 632226 reaction equation
[CH:1]1([B-](F)(F)F)[CH2:3][CH2:2]1.[K+].C(=O)([O-])[O-].[Cs+].[Cs+].Br[C:16]1[CH:17]=[CH:18][C:19]([C:29]([OH:31])=[O:30])=[N:20][C:21]=1[O:22][CH2:23][CH:24]1[CH2:28][CH2:27][CH2:26][O:25]1>C1(C)C=CC=CC=1.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(P(C12CC3CC(CC(C3)C1)C2)C12CC3CC(CC(C3)C1)C2)CCC>[CH:1]1([C:16]2[CH:17]=[CH:18][C:19]([C:29]([OH:31])=[O:30])=[N:20][C:21]=2[O:22][CH2:23][CH:24]2[CH2:28][CH2:27][CH2:26][O:25]2)[CH2:3][CH2:2]1

Participants

8

Reactant 3

HCID 10796Cesium carbonateHCID 23697338Potassium cyclopropyltrifluoroborateHCID 710877285-Bromo-6-(tetrahydro-furan-2-ylmethoxy)-pyridine-2-carboxylic acid

Product 1

HCID 710872545-Cyclopropyl-6-(tetrahydro-furan-2-ylmethoxy)-pyridine-2-carboxylic acidYield 36%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 11371790Bis(adamantan-1-yl)(butyl)phosphaneCatalystHCID 962WaterSolvent2×HCID 1140TolueneSolvent

Conditions

Temperature
120 °C

Procedure

Palladium(II)acetate (1.19 mg, 5.3 μmol), butylbis(tricyclo[3.3.1.13,7]dec-1-yl)-phosphine (2.85 mg, 7.94 μmol, CAN 321921-71-5), potassium cyclopropyltrifluoroborate (39.6 mg, 267 μmol) and cesium carbonate (259 mg, 794 μmol) were combined to give a white solid. To this solid a degassed solution of 5-bromo-6-(tetrahydro-furan-2-ylmethoxy)-pyridine-2-carboxylic acid (80 mg, 265 μmol) in toluene (2.02 mL)/water (224 μL) was added through a septum cap. The reaction mixture was heated to 120° C. and stirred for 20 h. After cooling to ambient temperature the reaction mixture was diluted with water (2 mL), poured onto 20 mL ice water/brine/1 N HCl, extracted with isopropyl acetate (2×40 mL), and washed with 20 mL ice water/brine. The organic layers were dried with Na2SO4 and concentrated in vacuo to give a light brown oily residue which was purified by preparative TLC (silica gel, 2.0 mm, DCM/MeOH, 49:1). The title compound (25 mg, 36%) was isolated as light yellow liquid; MS (ESI): 262.0 [M−H]−.

Workup

  1. customto give a white solid
  2. customcap
  3. temperatureAfter cooling to ambient temperature the reaction mixture
  4. extractionextracted with isopropyl acetate (2×40 mL)
  5. washwashed with 20 mL ice water/brine
  6. dry with materialThe organic layers were dried with Na2SO4
  7. concentrationconcentrated in vacuo
  8. customto give a light brown oily residue which
  9. customwas purified by preparative TLC (silica gel, 2.0 mm, DCM/MeOH, 49:1)

Sources & evidence

ORD record
ord-615d170423664c159ec739c99c748ac9
Source dataset
uspto-grants-2016_04
Patent number
US09321727B2

Linked notes

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