Tri-tert-butylphosphine tetrafluoroborate → HCID 57541245, compound

HRID 421740Notes

Reaction equation

HRID 421740 reaction equation
CC(C)([O-])C.[Na+].[CH3:7][N:8]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[S:9]([CH2:12][C:13](OC)=O)(=[O:11])=[O:10].BrC1[CH:25]=[CH:26][C:27]2[CH:38]=[CH:37][C:31]3=[N:32][CH:33]=[C:34]([Cl:36])[CH:35]=[C:30]3[C:29](=[O:39])[C:28]=2[CH:40]=1.F[B-](F)(F)F.C([PH+](C(C)(C)C)C(C)(C)C)(C)(C)C>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Cl:36][C:34]1[CH:35]=[C:30]2[C:29](=[O:39])[C:28]3[CH:40]=[C:13]([CH2:12][S:9]([N:8]([CH3:7])[C:17]4[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=4)(=[O:10])=[O:11])[CH:25]=[CH:26][C:27]=3[CH:38]=[CH:37][C:31]2=[N:32][CH:33]=1

Participants

7

Reactant 4

HCID 2734635Tri-tert-butylphosphine tetrafluoroborateHCID 14002850HCID 14002850, compoundHCID 159808187-Bromo-3-chloro-5H-benzo[4,5]cyclohepta[1,2-B]pyridin-5-oneHCID 23676156Sodium t-butoxide

Product 1

HCID 57541245HCID 57541245, compound

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

Sodium tert-butoxide (47.4 g, 493 mmol) was added in one portion to a 1 L flask containing methyl {[methyl(phenyl)amino]sulfonyl}acetate (40.0 g, 164 mmol) and dissolved in dioxane (658 ml) at 0° C. After 15 min., 7-bromo-3-chloro-5H-benzo[4,5]cyclohepta[1,2-b]pyridin-5-one (52.7 g, 164 mmol) was added followed by palladium(II) acetate (1.846 g, 8.22 mmol) and tri-t-butylphosphonium tetrafluoroborate (7.16 g, 24.66 mmol). The resulting suspension was degassed by sparging with nitrogen for 30 min. Then, the mixture was heated to 90° C. in a pre-warmed bath and left to stir for 1 h. Then, the reaction flask was cooled to 50° C., 1M NaOH (500 mL) was added and the solution was stirred for 1 h. Then, the solution was diluted with saturated aqueous sodium hydrogen carbonate (800 mL) and extracted with dichloromethane (3×500 mL). The combined organics were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by column chromatography (EtOAc/Hexanes gradient) to afford the title compound as a pale yellow solid. 1H NMR (600 MHz, DMSO-D6) δ 8.99 (d, 1H); 8.47 (m, 1H); 8.17 (s, 1H); 7.81 (s, 2H); 7.47 (d, 1H); 7.32 (m, 5H); 7.21 (m, 1H); 4.75 (s, 2H); 3.24 (s, 3H). LRMS (APCI) calculated for C22H18ClN2O3S [M+H]+, 425.1; found 425.0.

Workup

  1. customThe resulting suspension was degassed
  2. customby sparging with nitrogen for 30 min
  3. waitleft
  4. temperatureThen, the reaction flask was cooled to 50° C.
  5. addition1M NaOH (500 mL) was added
  6. stirringthe solution was stirred for 1 h
  7. additionThen, the solution was diluted with saturated aqueous sodium hydrogen carbonate (800 mL)
  8. extractionextracted with dichloromethane (3×500 mL)
  9. dry with materialThe combined organics were dried over anhydrous Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure
  12. customThe residue was purified by column chromatography (EtOAc/Hexanes gradient)

Sources & evidence

ORD record
ord-edbd1eda5c05467d8d1799a742928cb3
Source dataset
uspto-grants-2012_01
Patent number
US08101603B2

Reaction notes

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