2-Bromo-3-fluoropyridine → HCID 117814864, compound

HRID 634541Notes

Reaction equation

HRID 634541 reaction equation
C([Mg]Cl)(C)C.Br[C:7]1[C:12]([F:13])=[CH:11][CH:10]=[CH:9][N:8]=1.[Cl:14][C:15]1[N:20]=[C:19](I)[C:18]([NH2:22])=[CH:17][CH:16]=1>O1CCCC1.[Cl-].[Zn+2].[Cl-].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:14][C:15]1[N:20]=[C:19]([C:7]2[C:12]([F:13])=[CH:11][CH:10]=[CH:9][N:8]=2)[C:18]([NH2:22])=[CH:17][CH:16]=1

Participants

7

Reactant 3

HCID 27628032-Bromo-3-fluoropyridineHCID 184070436-Chloro-2-iodopyridin-3-amineHCID 178418918HCID 178418918, compound

Product 1

HCID 117814864HCID 117814864, compoundYield 69%

Reagents, catalysts & solvents 3

HCID 3007855ZincchlorideCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

A 3-neck 1000 mL RBF was dried under vacuum, then charged with isopropylmagnesium chloride (78 mL, 156 mmol) and cooled with a water bath. 2-bromo-3-fluoropyridine (14.37 mL, 142 mmol) was added dropwise making sure temperature did not exceed 30° C. The reaction was stirred at room temperature overnight, then treated dropwise with zinc(II) chloride (341 mL, 170 mmol) over 3 hrs and stirred at room temperature overnight. This suspension was then added dropwise via canula to a degassed, 65° C. solution of Pd(PPh3)4 (8.21 g, 7.10 mmol) and 6-chloro-2-iodopyridin-3-amine (39.8 g, 156 mmol) in tetrahydrofuran (THF) (Volume: 474 mL) and heated at reflux overnight. After cooled to room temperature, the reaction was quenched with sat. aq. NaHCO3 and water. The precipitate was filtered out and washed with EtOAc. The filtrate was extracted with EtOAc. The crude product was purified by column chromatography in 40-50% EtOAc/hexanes with column conditioned in 20% TEA/hexanes to give 6-chloro-3′-fluoro-[2,2′-bipyridin]-3-amine (21.8 g, 69% yield).

Workup

  1. customA 3-neck 1000 mL RBF was dried under vacuum
  2. temperaturecooled with a water bath
  3. customdid not exceed 30° C
  4. stirringstirred at room temperature overnight
  5. temperatureheated
  6. temperatureat reflux overnight
  7. temperatureAfter cooled to room temperature
  8. customthe reaction was quenched with sat. aq. NaHCO3 and water
  9. filtrationThe precipitate was filtered out
  10. washwashed with EtOAc
  11. extractionThe filtrate was extracted with EtOAc
  12. customThe crude product was purified by column chromatography in 40-50% EtOAc/hexanes with column

Sources & evidence

ORD record
ord-ebbb77b78c98425683e9f917b7c44fd4
Source dataset
uspto-grants-2016_04
Patent number
US09324949B2

Reaction notes

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