Sodium Carbonate → HCID 57827526, compound

HRID 1693258Notes

Reaction equation

HRID 1693258 reaction equation
[F:1][C:2]1[C:7](B(O)O)=[CH:6][CH:5]=[CH:4][N:3]=1.C(=O)([O-])[O-].[Na+].[Na+].Br[C:18]1[C:19]([F:46])=[CH:20][C:21]([F:45])=[C:22]([C@:24]23[CH2:33][CH2:32][CH2:31][CH2:30][C@H:29]2[CH2:28][S:27][C:26]([NH:34]C(=O)OCC2C=CC=CC=2)=[N:25]3)[CH:23]=1.I[Si](C)(C)C.C(=O)(O)[O-].[Na+]>C1(C)C=CC=CC=1.C(Cl)(Cl)Cl.C(OCC)(=O)C.S([O-])([O-])(=O)=S.[Na+].[Na+].C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C(O)(C)C>[F:45][C:21]1[CH:20]=[C:19]([F:46])[C:18]([C:7]2[C:2]([F:1])=[N:3][CH:4]=[CH:5][CH:6]=2)=[CH:23][C:22]=1[C@:24]12[CH2:33][CH2:32][CH2:31][CH2:30][C@H:29]1[CH2:28][S:27][C:26]([NH2:34])=[N:25]2

Participants

12

Reactant 5

HCID 10340Sodium CarbonateHCID 85247Trimethylsilyl iodideHCID 516892Sodium BicarbonateHCID 27832702-Fluoropyridine-3-boronic acidHCID 57827152HCID 57827152, compound

Product 1

HCID 57827526HCID 57827526, compoundYield 7.5%

Reagents, catalysts & solvents 6

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolventHCID 3776IsopropanolSolventHCID 6212ChloroformSolventHCID 8857Ethyl AcetateSolventHCID 24477Sodium ThiosulfateSolvent

Conditions

Temperature
85 °C

Procedure

Isopropyl alcohol (1 mL), 2-fluoro-3-pyridineboronic acid (49.8 mg), a 1 N sodium carbonate solution (354 μL) and bis(tri-tert-butylphosphine)palladium (0) (3.61 mg) were added to a solution of benzyl(±)-[(4aR*,8aS)-8a-(5-bromo-2,4-difluorophenyl)-4a,5,6,7,8,8a-hexahydro-4H-benzo[d][1,3]thiazin-2-yl]carbamate (35 mg) in toluene (2 mL). After replacement with nitrogen, the mixture was stirred at 85° C. for 9.5 hours. The reaction solution was cooled to room temperature, and the solvent was evaporated under reduced pressure. The residue was purified by NH-silica gel column chromatography to obtain an intermediate. The resulting intermediate was dissolved in chloroform (2 mL). Iodotrimethylsilane (30 μL) was added, followed by stirring for 14 hours. The reaction solution was returned to room temperature, and a sodium bicarbonate solution was added to the reaction mixture. The mixture was diluted with ethyl acetate and sodium thiosulfate was added, followed by stirring for 30 minutes. The reaction mixture was extracted with ethyl acetate when it became transparent. The organic layer was washed with brine. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was sequentially purified by NH-pTLC and pTLC to obtain the title compound (2.0 mg).

Workup

  1. temperatureThe reaction solution was cooled to room temperature
  2. customthe solvent was evaporated under reduced pressure
  3. customThe residue was purified by NH-silica gel column chromatography
  4. customto obtain an intermediate
  5. stirringby stirring for 14 hours
  6. customwas returned to room temperature
  7. additionwas added
  8. stirringby stirring for 30 minutes
  9. extractionThe reaction mixture was extracted with ethyl acetate when it
  10. washThe organic layer was washed with brine
  11. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  12. customthe solvent was evaporated under reduced pressure
  13. customThe residue was sequentially purified by NH-pTLC

Sources & evidence

ORD record
ord-e90c190e86644df995496400eb32e60a
Source dataset
uspto-grants-2012_04
Patent number
US08158620B2

Reaction notes

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