Reacción #65996

Ecuación de reacción

HCl

N-methylhydroxylamine hydrochloride

oxalyl chloride

compound

1-[(Phenyl)methyl]-2-methyl-5-[(2-phenyl-4-thiazolyl)methoxy]-1H-indole-3-acetic acid

→

white crystalline product

Rendimiento 57.0%

N-hydroxy-5-[(2-phenyl-4-thiazolyl)methoxy]-1-(phenylmethyl)-N,2-dimethyl-1H-indole-3-acetamide

Rendimiento 57.0%

Disolventes

methylene chloride

triethylamine

water

tetrahydrofuran

methylene chloride

methylene chloride

dimethylacetamide

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.STIRRINGAfter stirring at room temperature for 30 minutes
2. 2
   workup.ADDITIONthe reaction mixture is poured into a solution
3. 3
   workup.STIRRINGAfter stirring at room temperature for 1 hour
4. 4
   Otrothe layers are separated
5. 5
   LavadoThe aqueous layer is washed again with methylene chloride (100 mL)
6. 6
   ExtracciónThe combined methylene chloride extract
7. 7
   Lavadois washed with water (100 mL) and brine (100 mL)
8. 8
   Secadodried over MgSO4
9. 9
   Concentraciónconcentrated under reduced pressure
10. 10
    Otroto give 1.0 g of a crude solid
11. 11
    OtroThe solid is recrystallized from ether/methylene chloride

Procedimiento

A mixture of the compound of Example 40 (1.0 g, 2.13 mmol), methylene chloride (50 mL) and dimethylacetamide (0.15 mL) is cooled to 5° C. and with stirring, a solution of oxalyl chloride (0.45 mL, 5.3 mmol) in methylene chloride (10 mL) is added slowly. After stirring at room temperature for 30 minutes, the reaction mixture is poured into a solution containing tetrahydrofuran (11 mL), water (1.1 mL), triethylamine (1.8 mL) and N-methylhydroxylamine hydrochloride (0.7 g, 8.5 mmol). After stirring at room temperature for 1 hour, the reaction mixture is diluted with methylene chloride (150 mL), poured into 2N HCl (150 mL) and the layers are separated. The aqueous layer is washed again with methylene chloride (100 mL). The combined methylene chloride extract is washed with water (100 mL) and brine (100 mL), dried over MgSO4 and concentrated under reduced pressure to give 1.0 g of a crude solid. The solid is recrystallized from ether/methylene chloride to give 0.6 g of white crystalline product in 57 % yield, m.p. 171°-173° C.

Fuente