Lithium Chloride → 2-(6-Fluoropyridin-3-yl)pyrimidine

HRID 525404Notes

Reaction equation

HRID 525404 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([F:8])=[N:6][CH:7]=1.C([Sn](CCCC)(CCCC)[C:14]1[N:19]=[CH:18][CH:17]=[CH:16][N:15]=1)CCC.[Cl-].[Li+]>[Cu]I.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.CN(C=O)C>[F:8][C:5]1[N:6]=[CH:7][C:2]([C:14]2[N:19]=[CH:18][CH:17]=[CH:16][N:15]=2)=[CH:3][CH:4]=1

Participants

7

Reactant 3

HCID 433294Lithium ChlorideHCID 27632512-(Tributylstannyl)pyrimidineHCID 27831685-Bromo-2-fluoropyridine

Product 1

HCID 578217612-(6-Fluoropyridin-3-yl)pyrimidineYield 49%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

A microwave vial was charged with 5-bromo-2-fluoropyridine (commercially available from Acros, Pittsburgh, Pa.)(0.200 mL, 1.738 mmol), 2-(tributylstannyl)pyrimidine (commercially available from Frontier Scientific, Inc., Logan Utah) (0.718 mL, 2.173 mmol), lithium chloride (0.147 g, 3.48 mmol), copper (I) iodide (0.033 g, 0.174 mmol), and DMF (5.0 mL). Tetrakis(triphenylphosphine)palladium(0) (0.201 g, 0.174 mmol) was added, the system was purged with argon, and the tube was sealed. The resulting mixture was stirred at 120° C. in a microwave for 1 hour. The reaction mixture was then concentrated to afford a brown oil. The resulting oil was purified using column chromatography on silica gel (RediSep 40 g column, gradient elution with 0-25% EtOAc-heptane) to afford 2-(6-fluoropyridin-3-yl)pyrimidine (0.150 g, 0.856 mmol, 49% yield) as a pale yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 7.35 (dddd, J=8.51, 7.65, 2.91, 0.59 Hz, 1H), 7.54 (t, J=4.89 Hz, 1H), 8.28-8.43 (m, 1H), 8.78-8.89 (m, 1H), 8.96 (d, J=4.89 Hz, 2H). m/z (ESI) 176(M+H)+.

Workup

  1. customthe system was purged with argon
  2. customthe tube was sealed
  3. concentrationThe reaction mixture was then concentrated
  4. customto afford a brown oil
  5. customThe resulting oil was purified

Sources & evidence

ORD record
ord-240cd9a142a3459088926b488361d921
Source dataset
uspto-grants-2016_05
Patent number
US09340549B2

Reaction notes

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