反応 #48874

反応方程式

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

BEMP

potassium benzoate

4-fluoroacetophenone

→

desired product

収率 49.8%

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

収率 49.8%

溶媒

NMP

反応条件

後処理

1. 1
   ろ過was filtered off
2. 2
   洗浄the resin washed with ethyl acetate (100 mL)
3. 3
   workup.ADDITIONto be added
4. 4
   洗浄The aqueous phase was washed twice with ethyl acetate (50 mL)
5. 5
   洗浄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)
6. 6
   乾燥dried (MgSO4)
7. 7
   その他The volatiles were removed
8. 8
   その他the resulting oil purified by on silica
9. 9
   洗浄eluting with 0-100% ethyl acetate in iso-hexane

実験手順

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).

出典