Formaldehyde → 2-Hydroxy-5-methoxybenzaldehyde

Temperature

45 °C

A mixture of 600 g of acetonitrile, 186.2 g of 4-methoxyphenol (1.5 moles) and 214 g (2.25 moles) of anhydrous magnesium chloride was warmed to 45° C. and 227.4 g (2.25 moles) of triethylamine was added dropwise at that temperature. Paraformaldehyde (150 g, 4.75 moles) was then added and the reaction was heated to reflux. Methanol was removed over 3 hours by distillation, using a 10-inch column packed with Penn-State packing. The weight of the methanol removed (vapor temperature 60-65° C.) was 130 g. The solution was cooled to 60° C. and added to 900 mL of water. The solution was acidified with 240 mL of conc. HCl and extracted with 150 g of ethyl acetate. The ethyl acetate solution was washed once with 300 mL of tap water, clarified through diatomaceous earth, and stripped on a rotary evaporator at 10 mm pressure and 85° C. bath temperature. The weight of the product was 206.5 g, the liquid chromatograph area percent was 86%, and liquid chromatograph weight percent was 82%. The overall assay yield was 74%.

1. temperaturethe reaction was heated to reflux
2. customMethanol was removed over 3 hours by distillation
3. customThe weight of the methanol removed (vapor temperature 60-65° C.)
4. temperatureThe solution was cooled to 60° C.
5. additionadded to 900 mL of water
6. extractionextracted with 150 g of ethyl acetate
7. washThe ethyl acetate solution was washed once with 300 mL of tap water
8. customstripped on a rotary evaporator at 10 mm pressure and 85° C. bath temperature

ORD record

ord-ff4a6282f0b54a97b5ce4605fd6d4f15

Source dataset

uspto-grants-2003_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06670510B2