反应详情

温度

60 °C

The crude solid trifluoroacetophenone from Step 1 (11.54 kg) is dissolved in 48 L of ethanol and is charged into a 100 L round-bottom flask. Water (8L) is then added. Hydroxylamine hydrochloride (NH2OH.HCl, 11.05 kg) is added to the stirred mixture, followed by the addition of NaHCO3 (13.36 kg). The heterogeneous solution is stirred at 60° C. overnight. The reaction is complete within 24 hours by LC assay. Work-up consists of the addition of 40L of water and 25L of toluene, followed by transfer to an extractor. The flask is rinsed with an additional 25L of toluene, which is also transferred to the extractor. The layers are separated, and the organic layer is extracted with one washing of 60L of 1N NaOH. The layers are separated, and the NaOH layer is neutralized with 12N HCL to pH=6.1. The aqueous layer is then extracted with 60L of toluene. The layers are separated and the aqueous layer is extracted a second time with toluene. The combined organic layers are washed with 4L of water. The organic layer is concentrated to a crude solid which can be used in the next step without further purification. Alternatively, the product can be crystallized from a toluene/heptane mixture. The product is predominantly the E oxime (shown in the equation above) rather than the Z oxime and is obtained in 85% yield from 2,4-dipropylresorcinol.

1. additionis charged into a 100 L round-bottom flask
2. waitThe reaction is complete within 24 hours by LC assay
3. washThe flask is rinsed with an additional 25L of toluene, which
4. customThe layers are separated
5. extractionthe organic layer is extracted with one
6. washwashing of 60L of 1N NaOH
7. customThe layers are separated
8. extractionThe aqueous layer is then extracted with 60L of toluene
9. customThe layers are separated
10. extractionthe aqueous layer is extracted a second time with toluene
11. washThe combined organic layers are washed with 4L of water
12. concentrationThe organic layer is concentrated to a crude solid which
13. customcan be used in the next step without further purification
14. customAlternatively, the product can be crystallized from a toluene/heptane mixture