Sulfuric Acid → Propan-2-yl 4,5,6-trichloropicolinate

HRID 75094Notes

Reaction equation

HRID 75094 reaction equation
[Cl:1][C:2]1[C:7]([Cl:8])=[C:6]([Cl:9])[N:5]=C(C(OC)=O)[CH:3]=1.S(=O)(=O)(O)O.[CH3:19][CH2:20][O:21][C:22]([CH3:24])=[O:23].[C:25]([O-])(O)=O.[Na+]>CC(O)C>[Cl:1][C:2]1[C:7]([Cl:8])=[C:6]([Cl:9])[N:5]=[C:24]([C:22]([O:21][CH:20]([CH3:25])[CH3:19])=[O:23])[CH:3]=1

Participants

6

Reactant 4

HCID 1118Sulfuric AcidHCID 8857Ethyl AcetateHCID 516892Sodium BicarbonateHCID 12993691Methyl 4,5,6-trichloropicolinate

Product 1

HCID 71551715Propan-2-yl 4,5,6-trichloropicolinate

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

Methyl 4,5,6-trichloropicolinate (prepared as in Balko, T. W. et al. U.S. Pat. No. 6,784,137 B2, Aug. 31, 2004; 14.19 g, 59.0 mmol) was slurried in 2-propanol (150 mL) in a 250 mL round bottom flask equipped with a Dean-Stark trap and a reflux condenser. Sulfuric acid (98% H2SO4; 8.07 g, 82 mmol) was added, and the reaction mixture was heated to reflux. After 20 h at reflux, the majority of the 2-propanol (100 mL) was distilled overhead. The remaining reaction mixture solidified upon cooling to room temperature. The resulting solid was stirred with EtOAc (500 mL) and satd aq NaHCO3 (500 mL). The organic layer was separated, washed with satd aq NaCl, and then filtered through Celite. The organic extract was concentrated to 150 mL by rotary evaporation. Hexane (100 mL) was added, and the solution was stored at −20° C. overnight. Crystals were collected, washed with hexane and dried in air (7.58 g, mp 104.6-105.7° C.). A second crop was obtained by concentration of the filtrate to give a total of 10.36 g (65%): 1H NMR (400 MHz, DMSO-d6) δ 8.23 (s, 1H, pyridine H), 5.16 (septet, J=6.3 Hz, 1H, CHMe2), 1.34 (d, J=6.3 Hz, 6H, CHMe2); 13C{1H} NMR (101 MHz, CDCl3) δ 161.9 (CO2R), 150.6, 145.9, 145.0, 133.1, 125.4 (C3), 70.7 (CHMe2), 21.7 (Me). Anal. Calcd for C9H8Cl3NO2: C, 40.26; H, 3.00; N, 5.22. Found: C, 40.25; H, 3.02; N, 5.22.

Workup

  1. customequipped with a Dean-Stark trap and a reflux condenser
  2. temperaturethe reaction mixture was heated to reflux
  3. temperatureAfter 20 h at reflux
  4. distillationthe majority of the 2-propanol (100 mL) was distilled overhead
  5. customThe remaining reaction mixture
  6. customThe organic layer was separated
  7. washwashed with satd aq NaCl
  8. filtrationfiltered through Celite
  9. extractionThe organic extract
  10. concentrationwas concentrated to 150 mL by rotary evaporation
  11. additionHexane (100 mL) was added
  12. customCrystals were collected
  13. washwashed with hexane
  14. customdried in air (7.58 g, mp 104.6-105.7° C.)
  15. customA second crop was obtained by concentration of the filtrate
  16. customto give a total of 10.36 g (65%)

Sources & evidence

ORD record
ord-f6325c44723b4d6090c40032527dfb06
Source dataset
uspto-grants-2014_09
Patent number
US08835409B2

Reaction notes

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