Sulfuric Acid → Ethyl 3-bromo-6-chloropicolinate

HRID 1483661Notes

Reaction equation

HRID 1483661 reaction equation
[Br:1][C:2]1[C:3]([C:9]([OH:11])=[O:10])=[N:4][C:5]([Cl:8])=[CH:6][CH:7]=1.S(=O)(=O)(O)O.[C:17]1(C)C=CC=C[CH:18]=1>C(O)C>[CH2:17]([O:10][C:9]([C:3]1[C:2]([Br:1])=[CH:7][CH:6]=[C:5]([Cl:8])[N:4]=1)=[O:11])[CH3:18]

Participants

5

Reactant 3

HCID 1118Sulfuric AcidHCID 1140TolueneHCID 269667323-Bromo-6-chloropyridine-2-carboxylic acid

Product 1

HCID 46738996Ethyl 3-bromo-6-chloropicolinate

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of 3-bromo-6-chloropicolinic acid (21, 8.0 g, 33.83 mmols) in a mixture of toluene (80 mL) and ethanol (40 mL) was added sulfuric acid (0.66 mL, 6.76 mmols). The reaction mixture was refluxed for 16 h, then allowed to cool, and partitioned between CHCl3 (200 mL) and saturated aq. NaHCO3 (250 mL). The aqueous layer was extracted with CHCl3 (2×100 mL), and the combined organic layers were dried over Na2SO4, filtered, and concentrated to give crude product which was purified by column chromatography (Silica gel 10% EtOAc in hexane) to yield title compound 22 (9.0 g, quantitative) as transparent oil. 1H NMR 400 MHz (DMSO-d6) δ: 8.31 (d, J=8.6 Hz, 1H), 7.68 (d, 1H, J=8.2 Hz), 4.39 (q, J=7.0 Hz, 2H), 1.33 (t, J=7.2 Hz, 3H).

Workup

  1. temperatureThe reaction mixture was refluxed for 16 h
  2. temperatureto cool
  3. custompartitioned between CHCl3 (200 mL) and saturated aq. NaHCO3 (250 mL)
  4. extractionThe aqueous layer was extracted with CHCl3 (2×100 mL)
  5. dry with materialthe combined organic layers were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto give crude product which
  9. customwas purified by column chromatography (Silica gel 10% EtOAc in hexane)

Sources & evidence

ORD record
ord-d10d5ae5f93547f2b5b3df16b18d4c40
Source dataset
uspto-grants-2016_08
Patent number
US09416146B2

Reaction notes

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