Reaktion #171643

Reaktionsgleichung

triethylamine

8-amino-N-(2-chlorophenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide HCl salt

8-(2-(benzyloxy)acetamido)-N-(2-chlorophenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide

BnOCH2COCl

→

158

Ausbeute 64.0%

N-(2-chlorophenyl)-8-(2-hydroxyacetamido)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide

Ausbeute 64.0%

Lösungsmittel

DCM

TFA

CF3SO3H

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.ADDITIONAfter the addition
2. 2
   Temperaturthe reaction mixture was raised to room temperature
3. 3
   workup.STIRRINGstirred for another 2 hours
4. 4
   SonstigeThe mixture was quenched by water
5. 5
   Extraktionextracted with EtOAc
6. 6
   Trocknendried over Na2SO4
7. 7
   Sonstigeevaporated to about 0.9 g of the crude product, which
8. 8
   Sonstigewas used for the next step without further purification
9. 9
   workup.STIRRINGwas stirred at 60° C. overnight
10. 10
    SonstigeAfter removal of the solvent
11. 11
    Sonstigethe crude product was purified by prep

Vorschrift

To a mixture of 8-amino-N-(2-chlorophenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide HCl salt (1.0 g, 2.37 mmol) in 30 mL of DCM (dichloromethane, methylene chloride) was added triethylamine (1 mL, 7.12 mmol). The mixture was stirred at 0° C. for 10 min and BnOCH2COCl (0.53 g, 2.85 mmol) was added dropwise. After the addition was completed, the reaction mixture was raised to room temperature and stirred for another 2 hours. The mixture was quenched by water and extracted with EtOAc. The organic phases were combined, dried over Na2SO4 and evaporated to about 0.9 g of the crude product, which was used for the next step without further purification. A mixture of 8-(2-(benzyloxy)acetamido)-N-(2-chlorophenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide (0.6 g, 1.13 mmol) in TFA (5 mL) and CF3SO3H (2 mL) was stirred at 60° C. overnight. After removal of the solvent, the crude product was purified by prep. TLC to give about 320 mg of 158 (isolated yield: 64%). 1H NMR (DMSO-d6, 400 MHz): δ 9.77 (s, 1H), 7.63-7.35 (m, 7H), 6.47 (s, 1H), 5.64 (s, 1H), 4.11 (s, 2H), 3.94 (d, J=5.2 Hz, 2H), 3.23 (s, 3H), 2.88 (d, J=5.2 Hz, 2H). MS: (ESI+) 443.0

Quelle