Dimethyl Sulfoxide → Methyl 3-formyl-4-nitrobenzoate

Temperature

-78 °C

In a 5-liter four-necked round-bottomed flask 1.5 l of methylene chloride was cooled to -78° C. Oxalyl chloride (164 g, 1.29 moles) was added slowly, followed by dropwise addition of 202 g (2.59 moles) of dry dimethylsulfoxide in 125 mL of methylene chloride, keeping the temperature below -70° C. After the addition was complete the reaction mixture was stirred at -78° C. for 30 minutes and 273 g (1.29 moles) of previously prepared methyl 3-hydroxymethyl-4-nitrobenzoate dissolved in 250 mL of methylene chloride was added dropwise. The reaction mixture was stirred an additional 30 minutes. Triethylamine (392 g 3.88 moles) in 125 mL of methylene chloride was added dropwise keeping the temperature below -65° C. The reaction mixture was warmed up slowly to room temperature and stirred overnight. The solvent was removed using a rotary evaporator and the resulting solid treated with a mixture of 2 l of ethyl acetate and 1 l of water. The organic phase was separated, filtered through diatomaceous earth, and washed sequentially with dilute aqueous hydrochloric acid (2×250 mL), water (2×250 mL), saturated aqueous sodium bicarbonate (2×250 mL), water (2×200 mL), brine (200 mL) and dried over anhydrous magnesium sulfate. The solvent was removed using a rotary evaporator. The crude reaction mixture was triturated with hexane and filtered yielding 234.1 g of the expected methyl 3-formyl-4-nitrobenzoate as a yellow solid. This compound was used as such in the next step.

1. customthe temperature below -70° C
2. additionAfter the addition
3. additionwas added dropwise
4. stirringThe reaction mixture was stirred an additional 30 minutes
5. customthe temperature below -65° C
6. temperatureThe reaction mixture was warmed up slowly to room temperature
7. stirringstirred overnight
8. customThe solvent was removed
9. customa rotary evaporator
10. additionthe resulting solid treated with a mixture of 2 l of ethyl acetate and 1 l of water
11. customThe organic phase was separated
12. filtrationfiltered through diatomaceous earth
13. washwashed sequentially with dilute aqueous hydrochloric acid (2×250 mL), water (2×250 mL), saturated aqueous sodium bicarbonate (2×250 mL), water (2×200 mL), brine (200 mL)
14. dry with materialdried over anhydrous magnesium sulfate
15. customThe solvent was removed
16. customa rotary evaporator
17. customThe crude reaction mixture
18. customwas triturated with hexane
19. filtrationfiltered

ORD record

ord-3e7ad0e7dba345acaa8ff9c6178599d3

Source dataset

uspto-grants-2000_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06140362