Hydrochloric Acid → 2-Fluoro-5-(thiophen-2-yl)pyridine

HRID 2172698Notes

Reaction equation

HRID 2172698 reaction equation
C1COCC1.Br[C:7]1[S:8][CH:9]=[CH:10][CH:11]=1.[F:12][C:13]1[N:18]=[CH:17][C:16]([Mg]Br)=[CH:15][CH:14]=1.Cl>Cl[Ni]1(Cl)[P](C2C=CC=CC=2)(C2C=CC=CC=2)CCC[P]1(C1C=CC=CC=1)C1C=CC=CC=1.C(OCC)C>[F:12][C:13]1[CH:14]=[CH:15][C:16]([C:7]2[S:8][CH:9]=[CH:10][CH:11]=2)=[CH:17][N:18]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 8028TetrahydrofuranHCID 138512-BromothiopheneHCID 178505837HCID 178505837, compound

Product 1

HCID 534159832-Fluoro-5-(thiophen-2-yl)pyridine

Reagents, catalysts & solvents 2

HCID 178418745HCID 178418745, compoundCatalystHCID 3283Diethyl EtherSolvent

Procedure

In a separate reaction vessel, under a nitrogen atmosphere were added NiCl2(dppp) (0.02 equiv, 0.60 g) and THF (50 ml). 2-Bromothiophene (8.1 g, 4.81 ml, 50 mmol, 1 equiv.) was added and the resulting solution stirred for 2 min. To the resulting mixture was then added the mixture prepared in STEP A above, over about 30 min at 0° C., then allowed to warm to room temperature, with stirring. To the resulting mixture was then added diethylether, then cooled to 0° C. and treated with 1N HCl. The resulting mixture was extracted with diethylether (3×), the layers separated, the organic layer dried over MgSO4, then filtered and the filtrate evaporated to yield 2-fluoro-5-(thiophen-2-yl)pyridine as a liquid residue.

Workup

  1. customIn a separate reaction vessel
  2. waitover about 30 min at 0° C.
  3. stirringwith stirring
  4. extractionThe resulting mixture was extracted with diethylether (3×)
  5. customthe layers separated
  6. dry with materialthe organic layer dried over MgSO4
  7. filtrationfiltered
  8. customthe filtrate evaporated

Sources & evidence

ORD record
ord-3970b077adca430b8727f9c56cc86ff3
Source dataset
uspto-grants-2015_06
Patent number
US09056850B2

Reaction notes

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