Reacción #87140

ord-0d56489e19764a699e9a2b26bc10f6cb

Disolventes

Condiciones de reacción

Condiciones detalladas
See reaction.notes.procedure_details.

Tratamiento posterior

  1. 1
    workup.STIRRINGThe mixture was stirred for another 1 h
  2. 2
    workup.STIRRINGThe reaction mixture was stirred at 50° C. for 4 h
  3. 3
    FiltraciónThe mixture was filtered
  4. 4
    workup.ADDITIONthe filtrate was poured into water (50 mL)
  5. 5
    ExtracciónThe resulting mixture was extracted with EtOAc (100 mL×3)
  6. 6
    Secadodried over anhydrous sodium sulfate
  7. 7
    Concentraciónconcentrated
  8. 8
    OtroThe residue was purified by flash column chromatography on silica gel (petroleum ether/EtOAc=15:1 to 3:1)

Procedimiento

Iodine (0.11 g, 0.43 mmol) was added to a mixture of (R)-methyl 2-(tert-butoxycarbonylamino)-3-iodopropanoate (1.30 g, 3.58 mmol) and zinc (0.620 g, 9.75 mmol) in DMF (30 mL). The mixture was stirred for 10 min and another portion of iodine (0.11 g, 0.43 mmol) was added. The mixture was stirred for another 1 h. 6-Bromo-2-(2,4-dimethoxybenzyl)-3,4-dihydro-2H-benzo[e][1,2]thiazine 1,1-dioxide (1.34 g, 3.25 mmol), Pd2(dba)3 (0.08 g, 0.09 mmol) and S—Phos (0.070 g, 0.17 mmol) were added. The reaction mixture was stirred at 50° C. for 4 h and then cooled to ambient temperature. The mixture was filtered and the filtrate was poured into water (50 mL). The resulting mixture was extracted with EtOAc (100 mL×3). The organic extracts were combined, dried over anhydrous sodium sulfate, and concentrated. The residue was purified by flash column chromatography on silica gel (petroleum ether/EtOAc=15:1 to 3:1) to afford (R)-methyl 2-((tert-butoxycarbonyl)amino)-3-(2-(2,4-dimethoxybenzyl)-1,1-dioxido-3,4-dihydro-2H-benzo[e][1,2]thiazin-6-yl)propanoate (0.8 g, 46% yield) as a yellow oil.

Fuente

DOI: 10.6084/m9.figshare.5104873.v1Patente: US09434761B2uspto-grants-2016_09