Formaldehyde → HCID 86606906, compound

Temperature

120 °C

3-Bromo-4-hydroxybenzoic acid (4-morpholinyl)amide (150 g, 0.524 mol), zinc cyanide (44.23 g, 0.341 mmol), zinc (0.90 g, 14 mmol) and 5% palladium-carbon (44.6 g, 0.021 mmol) are suspended in dimethylacetamide (1500 mL), and bubbled with nitrogen for 35 minutes. After further adding triphenylphosphine (22.0 g, 0.084 mmol) under nitrogen, the reaction mixture is heated at 120° C., and stirred for 4 hours. The mixture is cooled to 25° C., stirred overnight, and the insoluble materials are separated by filtration at room temperature. The active carbon is washed with dimethylacetamide (1V, 150 mL). In the following procedures, an aliquot is used, which is obtained by dividing the solution above equally into five aliquots. The solvent is evaporated so that 2V of dimethylacetamide remains. After adding toluene (180 mL 6V), conc. hydrochloric acid (0.71 w, 21.3 g) is added dropwise at 30° C. or below and bubbled with nitrogen at 25° C. for one hour. Toluene is evaporated until the concentration of hydrogen cyanide becomes 50 ppm or less (20 mmHg). After adding water (5.4V, 163 mL), 37% formalin (17 mL, 2 equiv.) is added at room temperature. The mixture is stirred overnight, and the amount of hydrogen cyanide in the gas phase is confirmed to be 5 ppm on a detection tube. After adding 37% formalin (17 mL, 2 equiv.), the mixture is stirred at 35° C. for one hour, and the amount of hydrogen cyanide in the gas phase is confirmed to be 1 ppm or below on a detection tube. The mixture is ice-cooled (4° C.) for one hour. The crystals are collected by filtration, washed with water (6V, 180 mL), aqueous 5% sodium bicarbonate (1V, 30 ml), and then water (2 v, 60 ml) (pH=7). The wet materials are suspended into acetone (1.5 V, 45 mL), stirred for 0.5 hours under reflux, cooled gradually, stirred at 5° C. for one hour under ice-cooling, and filtered. The resulting crystals are washed with 0.5V of acetone (15 mL), and dried with a conical dryer to give 3-cyano-4-hydroxybenzoic acid (4-morpholinyl)amide (20.06 g, yield: 82.4%, content: 98.1%). Mp: 238-240° C.

1. custombubbled with nitrogen for 35 minutes
2. temperatureThe mixture is cooled to 25° C.
3. stirringstirred overnight
4. customthe insoluble materials are separated by filtration at room temperature
5. washThe active carbon is washed with dimethylacetamide (1V, 150 mL)
6. customwhich is obtained
7. customThe solvent is evaporated so that 2V of dimethylacetamide
8. additionAfter adding toluene (180 mL 6V), conc. hydrochloric acid (0.71 w, 21.3 g)
9. additionis added dropwise at 30° C. or below
10. custombubbled with nitrogen at 25° C. for one hour
11. customToluene is evaporated until the concentration of hydrogen cyanide
12. additionis added at room temperature
13. stirringThe mixture is stirred overnight
14. stirringthe mixture is stirred at 35° C. for one hour
15. temperaturecooled (4° C.) for one hour
16. filtrationThe crystals are collected by filtration
17. washwashed with water (6V, 180 mL), aqueous 5% sodium bicarbonate (1V, 30 ml)
18. stirringstirred for 0.5 hours
19. temperatureunder reflux
20. temperaturecooled gradually
21. stirringstirred at 5° C. for one hour under ice-
22. temperaturecooling
23. filtrationfiltered
24. washThe resulting crystals are washed with 0.5V of acetone (15 mL)
25. customdried with a conical dryer

ORD record

ord-350630c5b8f14cc186693bb5cbb07349

Source dataset

uspto-grants-2008_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07439368B2