Reaktion #46945

Reaktionsgleichung

1-(2-hydroxy-5-methoxy-phenyl)-ethanone

1-(2-hydroxy-5-methoxy-phenyl)-ethanone

MeMgCl

MeMgCl

2-(1-hydroxy-1-methyl-ethyl)-4-methoxy-phenol

HCl

→

2-isopropyl-4-methoxyphenol

Lösungsmittel

water

THF

THF

THF

2-butanone

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigedid not exceed 25 degrees C
2. 2
   TemperaturThe reaction mixture was cooled
3. 3
   workup.ADDITIONwas added
4. 4
   Temperaturwhile maintaining the reaction temperature at 25° C
5. 5
   Filtrationfiltered through a bed of Celite
6. 6
   Sonstigeto remove
7. 7
   WaschenThe filter cake was rinsed with EtOAc
8. 8
   Sonstigethe combined filtrate was separated
9. 9
   WaschenThe organic phase was washed with water
10. 10
    Einengenconcentrated by distillation
11. 11
    Sonstigeto provide an oil
12. 12
    EinengenA 161.8 g aliquot of the solution was concentrated under vacuum

Vorschrift

To a cooled solution of 1-(2-hydroxy-5-methoxy-phenyl)-ethanone (10.0 kg) in 79.0 kg of THF was gradually added 46.4 kg of 3M solution of MeMgCl in THF at a rate such that the reaction mixture temperature did not exceed 25 degrees C. Following addition of the MeMgCl solution, the reaction mixture was stirred at ambient temperature for 18 hours, at which point HPLC analysis showed more than 98% conversion of 1-(2-hydroxy-5-methoxy-phenyl)-ethanone to 2-(1-hydroxy-1-methyl-ethyl)-4-methoxy-phenol (not shown in Scheme D). To the stirred solution was then added 10% palladium on carbon (1.02 kg, 50% water wet) suspended in 3.5 Kg of THF. The reaction mixture was cooled and placed under a hydrogen atmosphere at 5 psig, and concentrated HCl (19.5 kg) was added while maintaining the reaction temperature at 25° C. The resultant mixture was stirred at ambient temperature for 18 hours, then treated with 44.4 kg water and filtered through a bed of Celite to remove suspended catalyst. The filter cake was rinsed with EtOAc and the combined filtrate was separated. The organic phase was washed with water, then concentrated by distillation to provide an oil. This oil was dissolved in 2-butanone (20.4 kg) and the crude solution was employed directly in the next step. A 161.8 g aliquot of the solution was concentrated under vacuum to provide 49.5 g of 2-isopropyl-4-methoxyphenol as an oil, projecting to 10.4 kg crude contained product in the bulk 2-butanone solution. 1H nmr (DMSO) delta: 1.14 (d, 6H, J=6.9 Hz), 3.18 (septet, 1H, J=6.9 Hz), 3.65 (s, 3H), 6.56, (dd, 1H, J=8.6 Hz, 3.1 Hz), 6.67 (d, 1H, J=3.1 Hz), 6.69 (d, 1H, 8.6 Hz).

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