1,2-Dimethoxyethane → HCID 86671314, compound

HRID 1472897Notes

Reaction equation

HRID 1472897 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[CH:20]=[C:19]([C:21]([F:24])([F:23])[F:22])[CH:18]=[C:17]([CH3:25])[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>[CH3:25][C:17]1[N: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)[CH:20]=[C:19]([C:21]([F:24])([F:22])[F:23])[CH:18]=1

Participants

9

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 11430Potassium CarbonateHCID 27366262-Chloro-6-methyl-4-(trifluoromethyl)pyridineHCID 251342782-(Trifluoromethyl)pyridine-5-boronic Acid

Product 1

HCID 86671314HCID 86671314, compoundYield 303.9%

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 (644 mg, 3.37 mmol), 2-chloro-6-methyl-4-(trifluoromethyl)pyridine (600 mg, 3.07 mmol), bis(triphenylphosphine)palladium(II) chloride (108 mg, 0.153 mmol), and K2CO3 (848 mg, 6.14 mmol), followed by the addition of DME (9.0 mL), water (3.86 mL) and ethanol (2.57 mL). The mixture was heated in the microwave at 120° C. for 10 minutes. The combined reaction mixtures were added 200 mL EtOAc, and filtered through a celite pad. The filtrate was 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 80 g column, eluted with 0-40% EtOAc in Hexanes (35 mL/min) to provide the title compound (2.858 g, 9.33 mmol, 101% yield) as a yellow solid. MS (ESI+) m/z 307.1 (M+H); 1H NMR (300 MHz, DMSO-d6) δ 9.51 (d, J=2.1, 1H), 8.82 (ddd, J=8.4, 2.2, 0.5, 1H), 8.36 (s, 1H), 8.06 (dd, J=8.4, 0.5, 1H), 7.78 (s, 1H), 2.70 (s, 3H).

Workup

  1. customThe combined reaction mixtures
  2. filtrationfiltered through a celite pad
  3. washThe filtrate was washed with 200 mL water and 200 mL brine
  4. dry with materialThe organic phase was dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was chromatographed on a Grace Reveleris 80 g column
  8. washeluted with 0-40% EtOAc in Hexanes (35 mL/min)

Sources & evidence

ORD record
ord-6f83d3dae06d416d82531f3588903a5b
Source dataset
uspto-grants-2015_04
Patent number
US09012651B2

Reaction notes

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