1,2-Dimethoxyethane → HCID 68312661, compound

HRID 1472895Notes

Reaction equation

HRID 1472895 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.Cl[C:15]1[N:20]=[C:19]([CH3:21])[C:18]([O:22][CH3:23])=[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>[CH3:23][O: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 146587126-Chloro-3-methoxy-2-methylpyridineHCID 251342782-(Trifluoromethyl)pyridine-5-boronic Acid

Product 1

HCID 68312661HCID 68312661, compoundYield 186.1%

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 (666 mg, 3.49 mmol), 6-chloro-3-methoxy-2-methylpyridine (500 mg, 3.17 mmol), bis(triphenylphosphine)palladium(II) chloride (111 mg, 0.159 mmol), and K2CO3 (877 mg, 6.35 mmol), followed by the addition of DME (9.0 mL), water (3.86 mL) and ethanol (2.57 mL). The mixture was heated on 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 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 (1.583 g, 5.90 mmol, 62.0% yield) as a white solid. MS (ESI+) m/z 269.1 (M+H); 1H NMR (300 MHz, DMSO-d6) δ 9.37 (d, J=1.8, 1H), 8.64 (dd, J=8.3, 1.9, 1H), 8.03 (d, J=8.6, 1H), 7.97 (d, J=8.3, 1H), 7.50 (d, J=8.6, 1H), 3.90 (s, 3H), 2.47 (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-9b709323be3c46e190c08afb809a0f84
Source dataset
uspto-grants-2015_04
Patent number
US09012651B2

Reaction notes

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