Diisopropylethylamine → 6-(2,6-Difluorophenyl)-3-fluoro-2-methylpyridine

HRID 1523510Notes

Reaction equation

HRID 1523510 reaction equation
Br[C:2]1[N:7]=[C:6]([CH3:8])[C:5]([F:9])=[CH:4][CH:3]=1.[F:10][C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([F:17])[C:12]=1B(O)O.CCN(C(C)C)C(C)C>C(O)C.C1(C)C=CC=CC=1.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>[F:10][C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([F:17])[C:12]=1[C:2]1[N:7]=[C:6]([CH3:8])[C:5]([F:9])=[CH:4][CH:3]=1

Participants

7

Reactant 3

HCID 81531DiisopropylethylamineHCID 27343362,6-Difluorophenylboronic acidHCID 27831806-Bromo-3-fluoro-2-methylpyridine

Product 1

HCID 592265276-(2,6-Difluorophenyl)-3-fluoro-2-methylpyridineYield 88%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 1140TolueneSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of 6-bromo-3-fluoro-2-methylpyridine (1.0 equiv.) in ethanol and toluene (1:1, 0.2 M) was added 2,6-difluorophenylboronic acid, DIEA (5 equiv.) and Pd(PPh3)4 (0.2 equiv.). The reaction was heated in the microwave at 120° C. for 30 min. The solution was filtered and rinsed with ethyl acetate. The volatiles were removed in vacuo and the crude was purified via silica gel column chromatography eluting with ethyl acetate and hexanes (2.5-20% ethyl acetate). Upon concentration of the pure fractions, 6-(2,6-difluorophenyl)-3-fluoro-2-methylpyridine was isolated in 88% yield. LC/MS=224.1 (M+H), Rt=0.87 min.

Workup

  1. filtrationThe solution was filtered
  2. washrinsed with ethyl acetate
  3. customThe volatiles were removed in vacuo
  4. customthe crude was purified via silica gel column chromatography
  5. washeluting with ethyl acetate and hexanes (2.5-20% ethyl acetate)

Sources & evidence

ORD record
ord-02aa5cf7bcca4d1d9d0eb650e81d81bf
Source dataset
uspto-grants-2015_07
Patent number
US09079889B2

Reaction notes

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