Hexane → Propan-2-yl 4-amino-3-chloro-5-fluoro-6-(4-chloro-2-fluoro-3-methoxyphenyl)picolinate

HRID 1913933Notes

Reaction equation

HRID 1913933 reaction equation
[NH2:1][C:2]1[C:7]([F:8])=[C:6]([C:9]2[CH:14]=[CH:13][C:12]([Cl:15])=[C:11]([O:16][CH3:17])[C:10]=2[F:18])[N:5]=[C:4]([C:19]([O:21][CH:22]([CH3:24])[CH3:23])=[O:20])[CH:3]=1.CCCCCC.S(Cl)([Cl:34])(=O)=O>>[NH2:1][C:2]1[C:7]([F:8])=[C:6]([C:9]2[CH:14]=[CH:13][C:12]([Cl:15])=[C:11]([O:16][CH3:17])[C:10]=2[F:18])[N:5]=[C:4]([C:19]([O:21][CH:22]([CH3:24])[CH3:23])=[O:20])[C:3]=1[Cl:34]

Participants

4

Reactant 3

HCID 8058HexaneHCID 24648Sulfuryl chlorideHCID 70497595Isopropyl 4-(amino)-6-(4-chloro-2-fluoro-3-methoxyphenyl)-5-fluoro-picolinate

Product 1

HCID 70497161Propan-2-yl 4-amino-3-chloro-5-fluoro-6-(4-chloro-2-fluoro-3-methoxyphenyl)picolinateYield 58%

Procedure

Propan-2-yl 4-amino-5-fluoro-6-(4-chloro-2-fluoro-3-methoxyphenyl)picolinate (3.065 g, 8.59 mmol) was dissolved in sulfuryl chloride (150 mL). The solution was stirred under nitrogen at room temperature for 8 h. During this time, a white precipitate formed. Hexane (100 mL) was added, and the mixture was stored overnight at −20° C. The product was filtered, washed with hexane and then slurried in EtOAc (100 mL). The organic suspension was neutralized with satd aq NaHCO3 solution, which caused all solids to dissolve. The organic layer was separated and washed with 10% aq NaHSO3 solution and brine, dried (MgSO4), and concentrated under reduced pressure to give a white solid (1.962 g, 58%): mp 109-111° C.; 1H NMR (400 MHz, CDCl3) δ 7.25 (m, 2H), 5.32 (septet, J=6.3 Hz, 1H, CHMe2), 5.07 (br s, 2H), 3.97 (d, JF-H=1.0 Hz, 3H, OMe), 1.40 (d, J=6.3 Hz, 6H, CHMe2); 19F NMR (376 MHz, CDCl3) δ −128.16 (dd, JF-F=33.3 Hz, JF-H=2.5 Hz, phenyl F), −138.35 (d, JF-F=33.4 Hz, pyridine F5).

Workup

  1. customDuring this time, a white precipitate formed
  2. waitthe mixture was stored overnight at −20° C
  3. filtrationThe product was filtered
  4. washwashed with hexane
  5. dissolutionto dissolve
  6. customThe organic layer was separated
  7. washwashed with 10% aq NaHSO3 solution and brine
  8. dry with materialdried (MgSO4)
  9. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-4b2366b683f8485f92ca0d89d7a6b26b
Source dataset
uspto-grants-2013_12
Patent number
US08609855B2

Reaction notes

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