Water → Propan-2-yl 4-amino-3,6-dichloro-5-fluoropicolinate

HRID 1913930Notes

Reaction equation

HRID 1913930 reaction equation
[NH2:1][C:2]1[C:7]([F:8])=[C:6]([Cl:9])[N:5]=[C:4]([C:10]([O:12][CH:13]([CH3:15])[CH3:14])=[O:11])[CH:3]=1.[Cl:16]N1C(C)(C)C(=O)N(Cl)C1=O.O>C(#N)C>[NH2:1][C:2]1[C:7]([F:8])=[C:6]([Cl:9])[N:5]=[C:4]([C:10]([O:12][CH:13]([CH3:15])[CH3:14])=[O:11])[C:3]=1[Cl:16]

Participants

5

Reactant 3

HCID 962WaterHCID 83601,3-Dichloro-5,5-dimethylhydantoin2×HCID 71551782Isopropyl 4-amino-6-chloro-5-fluoropicolinate

Product 1

HCID 71551839Propan-2-yl 4-amino-3,6-dichloro-5-fluoropicolinateYield 163.1%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Propan-2-yl 4-amino-6-chloro-5-fluoropicolinate (634 milligrams (mg), 2.73 mmol) was slurried in acetonitrile (11 mL). 1,3-Dichloro-5,5-dimethyl-hydantoin (303 mg, 1.54 mmol) was added as a solid, and the reaction mixture was stirred at reflux for 2.5 h. Additional 1,3-dichloro-5,5-dimethylhydantoin (50 mg, 0.25 mmol) was added, and the reaction mixture was stirred at reflux for an additional hour. Water (20 mL) was added. Acetonitrile was then removed by rotary evaporation to give an oily, yellow solid which was extracted with EtOAc (2×20 mL). The combined organic extracts were washed with 10% sodium bisulfite (NaHSO3) solution, satd aq NaHCO3 solution and brine, dried (MgSO4) and concentrated under reduced pressure to provide a pale orange solid (671 mg, 92%): 1H NMR (400 MHz, CDCl3) δ 5.29 (septet, J=6.3 Hz, 1H, CHMe2), 5.19 (br s, 2H, NH2), 1.40 (d, J=6.3 Hz, 6H, CHMe2); 19F NMR (376 MHz, CDCl3) δ −136.5.

Workup

  1. temperatureat reflux for 2.5 h
  2. stirringthe reaction mixture was stirred
  3. temperatureat reflux for an additional hour
  4. customAcetonitrile was then removed by rotary evaporation
  5. customto give an oily, yellow solid which
  6. extractionwas extracted with EtOAc (2×20 mL)
  7. washThe combined organic extracts were washed with 10% sodium bisulfite (NaHSO3) solution
  8. dry with materialdried (MgSO4)
  9. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-aea2e0a654ae4a208190d8652789503f
Source dataset
uspto-grants-2013_12
Patent number
US08609855B2

Reaction notes

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