1,2-Dimethoxyethane → HCID 68312317, compound

HRID 1472892Notes

Reaction equation

HRID 1472892 reaction equation
[F:1][C:2]([F:13])([F:12])[C:3]1[N:8]=[CH:7][C:6](B(O)O)=[CH:5][CH:4]=1.Br[C:15]1[C:20]([F:21])=[CH:19][CH:18]=[C:17]([CH3:22])[N:16]=1.C([O-])([O-])=O.[K+].[K+].COCCOC>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.CCOC(C)=O.C(O)C.O>[F:21][C:20]1[C:15]([C:6]2[CH:7]=[N:8][C:3]([C:2]([F:13])([F:12])[F:1])=[CH:4][CH:5]=2)=[N:16][C:17]([CH3:22])=[CH:18][CH:19]=1

Participants

9

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 11430Potassium CarbonateHCID 248203182-Bromo-3-fluoro-6-methylpyridineHCID 251342782-(Trifluoromethyl)pyridine-5-boronic Acid

Product 1

HCID 68312317HCID 68312317, compoundYield 284%

Reagents, catalysts & solvents 4

HCID 178418476HCID 178418476, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

A 20 mL microwave vial was charged with 6-(trifluoromethyl)pyridin-3-ylboronic acid (553 mg, 2.89 mmol), 2-bromo-3-fluoro-6-methylpyridine (500 mg, 2.63 mmol), bis(triphenylphosphine)palladium(II) chloride (92 mg, 0.132 mmol), and K2CO3 (727 mg, 5.26 mmol), followed by the addition of DME (9.0 mL), water (3.86 mL) and ethanol (2.57 mL). The reaction mixture was heated in the microwave at 120° C. for 10 minutes. To the reaction mixture was added 200 mL EtOAc, and washed with 200 mL water and 200 mL brine. The organic phase was separated, dried over Na2SO4, filtered, and concentrated. The residue was chromatographed on a Grace Reveleris 40 g column, eluted with 0-40% EtOAc in Hexanes (25 mL/min) to provide the title compound (7.47 mmol, 95% yield) as a white solid. MS (ESI+) m/z 257.1 (M+H); 1H NMR (300 MHz, DMSO-d6) δ 9.24 (s, 1H), 8.59-8.52 (m, 1H), 8.07 (d, J=8.2, 1H), 7.84 (dd, J=11.1, 8.5, 1H), 7.46 (dd, J=8.5, 3.5, 1H), 2.57 (s, 3H).

Workup

  1. washwashed with 200 mL water and 200 mL brine
  2. customThe organic phase was separated
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was chromatographed on a Grace Reveleris 40 g column
  7. washeluted with 0-40% EtOAc in Hexanes (25 mL/min)

Sources & evidence

ORD record
ord-41b73a8f97914cc18c994d1090a449f9
Source dataset
uspto-grants-2015_04
Patent number
US09012651B2

Reaction notes

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