Dimethylformamide → 3-Isopropyl-4-methoxybenzaldehyde

Temperature

80 °C

A 5 L three-necked round bottom flask was equipped with mechanical agitation and provided with an inert gas blanket. The flask was charged with 1-isopropyl-2-methoxybenzene (859 g, 5.85 moles) and dimethylformamide (1584 mL, 20.46 moles), and the mixture was heated to 80° C. Phosphorus oxychloride (2690 g, 17.54 moles) was added to the reaction mixture over approximately 3 h while maintaining the temperature of the reaction mixture between 80° C. and 90° C. The addition of POCl3 caused an immediate color change with continuous darkening over the course of the reaction. The reaction mixture was maintained at 80° C. for approximately 16 h, then checked by HPLC for presence of unreacted starting materials. The reaction mixture was quenched by slow addition over approximately 2 h to icewater (8 kg total, 5 kg ice); alternatively the reaction mixture was added over approximately 3 h to deionized water (10 L) in a jacketed 30 L reactor whose cooling bath was maintained between 0° and 5° C. Ethyl acetate (12 L) was added to the quenched reaction with stirring. After settling, the layers were separated, and the aqueous layer was washed with additional ethyl acetate (4 L). The combined organic layers were washed with saturated aqueous sodium bicarbonate solution (4 L) and saturated aqueous sodium chloride (4 L). The ethyl acetate was removed by vacuum distillation to yield 3-isopropyl-4-methoxybenzaldehyde (881 g, 86.5%).

1. customA 5 L three-necked round bottom flask was equipped with mechanical agitation
2. customprovided with an inert gas blanket
3. temperaturewhile maintaining the temperature of the reaction mixture between 80° C. and 90° C
4. customover the course of the reaction
5. temperatureThe reaction mixture was maintained at 80° C. for approximately 16 h
6. customThe reaction mixture was quenched by slow addition over approximately 2 h to icewater (8 kg total, 5 kg ice)
7. additionalternatively the reaction mixture was added over approximately 3 h to deionized water (10 L) in a jacketed 30 L reactor whose
8. temperaturecooling bath
9. temperaturewas maintained between 0° and 5° C
10. additionEthyl acetate (12 L) was added to the quenched reaction
11. customthe layers were separated
12. washthe aqueous layer was washed with additional ethyl acetate (4 L)
13. washThe combined organic layers were washed with saturated aqueous sodium bicarbonate solution (4 L) and saturated aqueous sodium chloride (4 L)
14. customThe ethyl acetate was removed by vacuum distillation

ORD record

ord-d678d797c1e942a9b51b1efb20459700

Source dataset

uspto-grants-2004_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06806381B2