Ethyl Acetate → HCID 44230475, compound

HRID 340188Notes

Reaction equation

HRID 340188 reaction equation
C(OC([NH:8]C1C=CC(C(OCC)=O)=CC=1B1OC(C)(C)C(C)(C)O1)=O)(C)(C)C.Br[C:30]1[C:31]([C:36]#[N:37])=[N:32][CH:33]=[CH:34][CH:35]=1.C(=O)([O-])[O-].[K+].[K+].[C:44]([O:47][CH2:48][CH3:49])(=[O:46])[CH3:45].[C:50]1(C)[CH:55]=[CH:54]C=[CH:52][CH:51]=1.C(O)C>CO.ClCCl.O.CCCCCC>[NH2:8][C:36]1[C:31]2[N:32]=[CH:33][CH:34]=[CH:35][C:30]=2[C:51]2[CH:52]=[C:45]([C:44]([O:47][CH2:48][CH3:49])=[O:46])[CH:54]=[CH:55][C:50]=2[N:37]=1

Participants

10

Reactant 5

HCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 8176943-Bromopyridine-2-carbonitrileHCID 21863594Toluene ethanolHCID 66893444HCID 66893444, compound

Product 1

HCID 44230475HCID 44230475, compound

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8058HexaneSolvent

Conditions

Temperature
100 °C

Procedure

A solution of ethyl 4-(tert-butoxycarbonylamino)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (from step 2) (1.0 eq.) and 3-bromopicolino-nitrile (1.0 eq.) in toluene/ethanol (10:1, 0.23 M) was mixed with tetrakis(triphenyl-phosphine)palladium (5 mol %) and anhydrous potassium carbonate (2.0 eq.). The reaction was heated to 100° C. and stiffed overnight. After cooling to ambient temperature, the reaction content was diluted with 2% methanol in dichloromethane and water. The two phases were separated, and the aqueous layer was extracted twice with 2% methanol in dichloromethane. The combined organic layers were washed with brine, dried over anhydrous MgSO4, and concentrated en vacuo. The crude material was purified by flash chromatography on a COMBIFLASH® system (ISCO) using 0-40% ethyl acetate in toluene to give a semipure solid, which was then swirled in hot 10% ethyl acetate in hexane, filtered, and dried to give a pure solid. 1H NMR (acetone d-6): δ 9.11 (d, 1H), 9.05 (s, 1H), 8.95 (d, 1H), 8.14 (d, 1H), 7.89-7.92 (dd, 1H), 7.63 (d, 1H), 4.38 (q, 2H), 1.40 (t, 3H). LRMS [M+H]=268.2.

Workup

  1. temperatureAfter cooling to ambient temperature
  2. customThe two phases were separated
  3. extractionthe aqueous layer was extracted twice with 2% methanol in dichloromethane
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over anhydrous MgSO4
  6. concentrationconcentrated en vacuo
  7. customThe crude material was purified by flash chromatography on a COMBIFLASH® system (ISCO)
  8. customto give a semipure solid, which
  9. filtrationfiltered
  10. customdried
  11. customto give a pure solid

Sources & evidence

ORD record
ord-40eda2ccb9cc4e5eb1544063cee6d6b1
Source dataset
uspto-grants-2014_11
Patent number
US08895577B2

Reaction notes

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