Water → (E)-4-amino-6-(4-chloro-3-fluorophenyl)-5-fluoro-3-(2-(trimethylsilyl)vinyl)picolinic acid

HRID 244325Notes

Reaction equation

HRID 244325 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]([F:16])[CH:10]=2)[N:5]=[C:4]([C:17]([O:19]C)=[O:18])[C:3]=1/[CH:21]=[CH:22]/[Si:23]([CH3:26])([CH3:25])[CH3:24].C1COCC1.O.O.[OH-].[Li+]>CO>[NH2:1][C:2]1[C:7]([F:8])=[C:6]([C:9]2[CH:14]=[CH:13][C:12]([Cl:15])=[C:11]([F:16])[CH:10]=2)[N:5]=[C:4]([C:17]([OH:19])=[O:18])[C:3]=1/[CH:21]=[CH:22]/[Si:23]([CH3:24])([CH3:26])[CH3:25]

Participants

6

Reactant 4

HCID 962WaterHCID 8028TetrahydrofuranHCID 168937Lithium hydroxide, monohydrateHCID 70497566HCID 70497566, compound

Product 1

HCID 70498157(E)-4-amino-6-(4-chloro-3-fluorophenyl)-5-fluoro-3-(2-(trimethylsilyl)vinyl)picolinic acidYield 90%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

(E)-methyl 4-amino-6-(4-chloro-3-fluorophenyl)-5-fluoro-3-(2-(trimethylsilyl)vinyl)picolinate (169 mg, 0.426 mmol) was dissolved in methanol (2 mL), THF (2 mL) and Water (1 mL). Lithium hydroxide hydrate (93 mg, 2.216 mmol) was added. The reaction mixture was stirred at room temperature overnight. The reaction mixture was concentrated to dryness under vaccum. The resulting residue was partitioned between 1 N HCl and ethyl acetate. The aqueous phase was extracted three more times with ethyl acetate. The organic phases were combined, dried over magnesium sulfate, filtered, and concentrated under vacuum to provide the title compound as an off-white solid (146 mg, 0.381 mmol, 90% yield): 1H NMR (400 MHz, DMSO-d6) δ 0.17 (s, 9H), 6.26 (d, J=19.4 Hz, 1H), 6.49 (s, 2H), 6.93 (d, J=19.5 Hz, 1H), 7.68-7.83 (m, 2H), 7.88 (dd, J=10.9, 1.8 Hz, 1H); 19F NMR (376 MHz, DMSO-d6) δ −145.32 , −116.04 . ESIMS m/z 384 ([M+H]+).

Workup

  1. concentrationThe reaction mixture was concentrated to dryness under vaccum
  2. customThe resulting residue was partitioned between 1 N HCl and ethyl acetate
  3. extractionThe aqueous phase was extracted three more times with ethyl acetate
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-67933490192a4bf09ab0b6766ad5674a
Source dataset
uspto-grants-2014_02
Patent number
US08658568B2

Reaction notes

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