Reacción #605411

Ecuación de reacción

EDC

HOBT

NH2OTHP

(E)-3-{1′-(2-Phenyl-ethyl)-3,4-dihydro-4-oxo-spiro[2H-(1,3)-benzoxazine-2,4′-piperidin]-6-yl}-acrylic acid

→

(E)-3-{1′-(2-phenyl-ethyl)-3,4-dihydro-4-oxo-spiro[2H-(1,3)-benzoxazine-2,4′-piperidin]-6-yl}-N-hydroxy-acrylamide hydrochloride

Rendimiento 64.4%

Disolventes

DCM

Condiciones de reacción

Tratamiento posterior

1. 1
   OtroThe mixture was partitioned between DCM and 5% aqueous NaHCO3
2. 2
   Secadothe organic phase was dried over Na2SO4
3. 3
   Otroevaporated
4. 4
   OtroThe crude mixture was purified by column chromatography (eluent: DCM/MeOH 95:5)
5. 5
   workup.DISSOLUTIONThe resulting (E)-3-{1′-(2-phenyl-ethyl)-3,4-dihydro-4-oxo-spiro[2H-(1,3)-benzoxazine-2,4′-piperidin]-6-yl}-N-(tetrahydro-pyran-2-yloxy)-acrylamide was dissolved in DCM
6. 6
   workup.ADDITIONtreated with 4 M HCl in dioxane for 3 h
7. 7
   FiltraciónThe precipitate was filtered off
8. 8
   Lavadowashed with DCM

Procedimiento

(E)-3-{1′-(2-Phenyl-ethyl)-3,4-dihydro-4-oxo-spiro[2H-(1,3)-benzoxazine-2,4′-piperidin]-6-yl}-acrylic acid (240 mg, 0.612 mmol) was dissolved in DCM (20 ml) and TEA (0.17 ml, 1.23 mmol). EDC (169 mg, 0.88 mmol), HOBT (119 mg, 0.88 mmol) and NH2OTHP (86 mg, 0.74 mmol) were added and the mixture was stirred at RT overnight. The mixture was partitioned between DCM and 5% aqueous NaHCO3 and the organic phase was dried over Na2SO4 and evaporated. The crude mixture was purified by column chromatography (eluent: DCM/MeOH 95:5). The resulting (E)-3-{1′-(2-phenyl-ethyl)-3,4-dihydro-4-oxo-spiro[2H-(1,3)-benzoxazine-2,4′-piperidin]-6-yl}-N-(tetrahydro-pyran-2-yloxy)-acrylamide was dissolved in DCM and treated with 4 M HCl in dioxane for 3 h. The precipitate was filtered off and washed with DCM to give (E)-3-{1′-(2-phenyl-ethyl)-3,4-dihydro-4-oxo-spiro[2H-(1,3)-benzoxazine-2,4′-piperidin]-6-yl}-N-hydroxy-acrylamide hydrochloride (175 mg) as a white solid.

Fuente