Reacción #88020

Ecuación de reacción

4-(N-(tert-butoxycarbonyl)methylsulfonamido)-thiophene-2-carboxylic acid

(S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-hydroxyethyl)pyridine 1-oxide

EDC

→

(S)-4-(2-(4-(N-(tert-butoxycarbonyl)methylsulfonamido)thiophene-2-carbonyloxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 1-oxide

Rendimiento 32.2%

Disolventes

DCM

DCM

Condiciones de reacción

Tratamiento posterior

1. 1
   Otroreaction
2. 2
   Lavadowashed with 1N HCl
3. 3
   Extracciónthe aqueous phase was extracted with EtOAc
4. 4
   Secadothe combined organic layers were dried over sodium sulfate
5. 5
   OtroThe solvent was removed under vacuum
6. 6
   Otrothe crude was purified by flash chromatography on silica gel (DCM/MeOH=98/2)

Procedimiento

To a solution of 4-(N-(tert-butoxycarbonyl)methylsulfonamido)-thiophene-2-carboxylic acid (Int. 44) (100 mg, 0.311 mmol) in DCM (5 ml), (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-hydroxyethyl)pyridine 1-oxide (131 mg, 0.311 mmol), EDC (179 mg, 0.934 mmol) and DMAP (19.01 mg, 0.156 mmol) were added, and reaction was stirred at RT overnight. The mixture was diluted with DCM (10 ml) and washed with 1N HCl; the aqueous phase was extracted with EtOAc and the combined organic layers were dried over sodium sulfate. The solvent was removed under vacuum and the crude was purified by flash chromatography on silica gel (DCM/MeOH=98/2) affording (S)-4-(2-(4-(N-(tert-butoxycarbonyl)methylsulfonamido)thiophene-2-carbonyloxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 1-oxide (Int. 45) (72 mg, 0.100 mmol, MS/ESI+722.9 [MH]+).

Fuente