Réaction #87140

Équation de réaction

Iodine

(R)-methyl 2-(tert-butoxycarbonylamino)-3-iodopropanoate

6-Bromo-2-(2,4-dimethoxybenzyl)-3,4-dihydro-2H-benzo[e][1,2]thiazine 1,1-dioxide

S—Phos

iodine

→

(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

Rendement 46.0%

Solvants

DMF

Conditions de réaction

Traitement

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
   FiltrationThe mixture was filtered
4. 4
   workup.ADDITIONthe filtrate was poured into water (50 mL)
5. 5
   ExtractionThe resulting mixture was extracted with EtOAc (100 mL×3)
6. 6
   Séchagedried over anhydrous sodium sulfate
7. 7
   Concentrationconcentrated
8. 8
   AutreThe residue was purified by flash column chromatography on silica gel (petroleum ether/EtOAc=15:1 to 3:1)

Mode opératoire

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.

Source