Reacción #48874

Ecuación de reacción

3-hydroxy-5-[(1S)-2-methoxy-(1-methylethyl)oxy]-N-(1-methyl-1H-pyrazol-3-yl)benzamide

BEMP

potassium benzoate

4-fluoroacetophenone

→

desired product

Rendimiento 49.8%

3-(4-Acetylphenoxy)-5-[(1S)-2-methoxy-1-methylethoxy]-N-(1-methyl-1H-pyrazol-3-yl)benzamide

Rendimiento 49.8%

Disolventes

NMP

Condiciones de reacción

Tratamiento posterior

1. 1
   Filtraciónwas filtered off
2. 2
   Lavadothe resin washed with ethyl acetate (100 mL)
3. 3
   workup.ADDITIONto be added
4. 4
   LavadoThe aqueous phase was washed twice with ethyl acetate (50 mL)
5. 5
   LavadoThe combined organic extracts were Washed with saturated aqueous lithium chloride solution (2×100 mL), 2M sodium hydroxide solution (2×100 mL), water (2×100 mL), brine (100 mL)
6. 6
   Secadodried (MgSO4)
7. 7
   OtroThe volatiles were removed
8. 8
   Otrothe resulting oil purified by on silica
9. 9
   Lavadoeluting with 0-100% ethyl acetate in iso-hexane

Procedimiento

A mixture of 3-hydroxy-5-[(1S)-2-methoxy-(1-methylethyl)oxy]-N-(1-methyl-1H-pyrazol-3-yl)benzamide (400 mg, 1.31 mmol), PS-BEMP (2-tert-butylimino-2-diethylamino-1,3-dimethyl-perhydro-1,3,2-diaza-phosphorine, polymer-bound, loading 2.2 mmol/g) (894 mg, 1.97 mmol), potassium benzoate (210 mg, 1.31 mmol) and 4-fluoroacetophenone (0.160 mL, 1.31 mmol) in NMP (10 mL) was heated to 200° C. in a ‘Smith Creator’ microwave for 1 hour. The polymer supported base was filtered off and the resin washed with ethyl acetate (100 mL). The organic phase was partioned with water (100 mL) at which point brine had to be added to resolve the layers. The aqueous phase was washed twice with ethyl acetate (50 mL) and then discarded. The combined organic extracts were Washed with saturated aqueous lithium chloride solution (2×100 mL), 2M sodium hydroxide solution (2×100 mL), water (2×100 mL), brine (100 mL) and dried (MgSO4). The volatiles were removed and the resulting oil purified by on silica, eluting with 0-100% ethyl acetate in iso-hexane, to give the desired product as a colourless foam (276 mg).

Fuente