Methyl 5-bromopyridine-2-carboxylate → HCID 86674749, compound

HRID 627706Notes

Reaction equation

HRID 627706 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([C:8]([O:10][CH3:11])=[O:9])=[N:6][CH:7]=1.[Br-].[CH:13]1([Zn+])[CH2:15][CH2:14]1>C1COCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH:13]1([C:2]2[CH:3]=[CH:4][C:5]([C:8]([O:10][CH3:11])=[O:9])=[N:6][CH:7]=2)[CH2:15][CH2:14]1

Participants

6

Reactant 2

HCID 7016458Methyl 5-bromopyridine-2-carboxylateHCID 178419765HCID 178419765, compound

Product 1

HCID 86674749HCID 86674749, compoundYield 73.1%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
80 °C

Procedure

To a sealed tube were added methyl 5-bromopicolinate (700 mg, 3.24 mmol) in THF (10 ml). The reaction mixture was purged with Ar followed by addition of tetrakis(triphenylphosphine)palladium (187 mg, 0.162 mmol) and finally cyclopropylzinc bromide solution 0.5 m in tetrahydrofuran (7.78 mL, 3.89 mmol). The tube was sealed and heated to 80° C. for 1.5 hrs. Then it was diluted with water, and extracted with EtOAc. The organic layer was washed with brine and concentrated to give crude product. The crude material was purified by chromatography through a Redi-Sep pre-packed silica gel column (40 g), eluting with a gradient of 25% to 40% to 60% EtOAc in Heptane, to provide methyl 5-cyclopropylpicolinate (420 mg, 2.370 mmol, 73.1% yield) as off-white solid. MS m/z=178.2 (M+H).

Workup

  1. customThe reaction mixture was purged with Ar
  2. customThe tube was sealed
  3. extractionextracted with EtOAc
  4. washThe organic layer was washed with brine
  5. concentrationconcentrated
  6. customto give crude product
  7. customThe crude material was purified by chromatography through a Redi-Sep pre-packed silica gel column (40 g)
  8. washeluting with a gradient of 25% to 40% to 60% EtOAc in Heptane

Sources & evidence

ORD record
ord-7ec81350dc8c459aa9baafb27d9350b4
Source dataset
uspto-grants-2016_04
Patent number
US09309263B2

Reaction notes

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