1,2-Dimethoxyethane → HCID 68312478, compound

HRID 1472894Notes

Reaction equation

HRID 1472894 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[N:20]=[C:19]([CH3:21])[C:18]([CH3:22])=[CH:17][CH: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>[CH3:22][C:18]1[CH:17]=[CH:16][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:20][C:19]=1[CH3:21]

Participants

9

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 11430Potassium CarbonateHCID 251342782-(Trifluoromethyl)pyridine-5-boronic AcidHCID 457912776-Bromo-2,3-dimethylpyridine

Product 1

HCID 68312478HCID 68312478, compoundYield 294.4%

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 (564 mg, 2.96 mmol), 6-bromo-2,3-dimethylpyridine (500 mg, 2.69 mmol), bis(triphenylphosphine)palladium(II) chloride (94 mg, 0.134 mmol), and K2CO3 (743 mg, 5.37 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 a 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 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 (1.997 g, 7.92 mmol, 98% yield) as a white solid. MS (ESI+) m/z 253.2 (M+H); 1H NMR (300 MHz, DMSO-d6) δ 9.40 (d, J=1.9, 1H), 8.68 (dd, J=8.3, 1.7, 1H), 8.00 (d, J=8.3, 1H), 7.92 (d, J=7.9, 1H), 7.71 (d, J=7.9, 1H), 2.54 (s, 3H), 2.33 (s, 3H).

Workup

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

Sources & evidence

ORD record
ord-e5a557b3b8c84c7bb012058558861ce2
Source dataset
uspto-grants-2015_04
Patent number
US09012651B2

Reaction notes

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