Methyl Tributylstannyl Sulfide → Methyl 4-amino-6-chloro-5-fluoro-3-(methylthio)picolinate

HRID 407256

Reaction equation

HRID 407256 reaction equation
[NH2:1][C:2]1[C:7]([F:8])=[C:6]([Cl:9])[N:5]=[C:4]([C:10]([O:12][CH3:13])=[O:11])[C:3]=1I.C([Sn](CCCC)(CCCC)[S:20][CH3:21])CCC>[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Cu]I>[NH2:1][C:2]1[C:7]([F:8])=[C:6]([Cl:9])[N:5]=[C:4]([C:10]([O:12][CH3:13])=[O:11])[C:3]=1[S:20][CH3:21]

Participants

5

Reactant 2

HCID 11110497Methyl Tributylstannyl SulfideHCID 86668303Methyl 4-amino-6-chloro-5-fluoro-3-iodopicolinate

Product 1

HCID 86675417Methyl 4-amino-6-chloro-5-fluoro-3-(methylthio)picolinate

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 13169693Triphenylphosphine palladium dichlorideCatalyst

Conditions

Temperature
80 °C

Procedure

Methyl 4-amino-6-chloro-5-fluoro-3-iodopicolinate (1.5 g, 4.6 mmol), tri-n-butylmethylthiostannane (2.5 g, 7.3 mmol), his (triphenylphosphine) palladium (II) chloride (320 mg, 0.46 mmol) and copper (I) iodide (90 mg, 0.46 mmol) were combined 15 ml dry, deaerated DMF and heated to 80° C. After 3 h another 2.5 g portion of the stannane were added and heating was continued for 18 h. After cooling, the mixture was stirred with 25 ml 10% potassium bifluoride solution for 20 ml. The heterogeneous mixture was stirred with 100 ml ethyl acetate and filtered through diatomaceous earth to remove curdy solids. The separated organic phase was washed twice with 15 ml water, 15 ml sat. NaCl, dried (Na2SO3) and evaporated. The product was purified by silica gel chromatography eluting with a 0-25% ethyl acetate-DCM gradient. The gummy residue was stirred with hexane to produce the written product as a white solid, 800 mg. Mp: 75-77° C. 1H NMR (400 MHz, CDCl3) δ 5.35 (s, 2H), 3.96 (s, 3H), 2.33 (s, 3H). 19F NMR (376 MHz, CDCl3) δ −138.81. EIMS m/z 250.

Workup

  1. customdry
  2. additionAfter 3 h another 2.5 g portion of the stannane were added
  3. temperatureheating
  4. temperatureAfter cooling
  5. stirringThe heterogeneous mixture was stirred with 100 ml ethyl acetate
  6. filtrationfiltered through diatomaceous earth
  7. customto remove curdy solids
  8. washThe separated organic phase was washed twice with 15 ml water, 15 ml sat. NaCl
  9. dry with materialdried (Na2SO3)
  10. customevaporated
  11. customThe product was purified by silica gel chromatography
  12. washeluting with a 0-25% ethyl acetate-DCM gradient
  13. stirringThe gummy residue was stirred with hexane

Sources & evidence

ORD record
ord-6db71d26e3b54614ae953f66ae2e9360
Source dataset
uspto-grants-2014_06
Patent number
US08754229B2

Linked notes

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