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

HRID 2046870Notes

Reaction equation

HRID 2046870 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-af46105fa280425e8bb7ab4e5d873850
Source dataset
uspto-grants-2013_11
Patent number
US08592455B2

Reaction notes

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