Formaldehyde → HCID 86596996, compound

Temperature

17 °C

A 2-liter, 3-neck round bottom flask equipped with a nitrogen blanket, addition funnel, mechanical stirrer and thermocouple was charged with isopropylamine (425 mL, 5.0 mol). The addition funnel was charged with a pre-dissolved mixture of tris(hydroxymethyl)nitromethane (TN®)(377.75 g, 2.5 mol) in 37% aqueous formaldehyde (202.9 g, 2.5 mol) and the reactor contents cooled to 15 C with a cold water bath. The TN/formaldehyde solution was added dropwise to the isopropylamine over a period of 1.5 hours while maintaining an internal reaction temperature of 15-19° C. After the addition was complete, the cooling bath was removed. The mixture changed from a clear solution to a water/oil emulsion and slowly warmed to 34° C. over 40 minutes. A heating mantle was then used to warm the mixture to 70° C. for 5 hours. The reaction mass was then allowed to cool back to room temperature overnight. The reaction product had partially solidified to a yellow paste. Hexane (750 mL) was then added and the water was azeotropically removed. As the last of the water was removed, a white solid precipitated. The slurry was placed in the freezer overnight to complete crystallization. The white, crystalline hexahydropyrimidine product was recovered via filtration, 245 g, 39.9% of theory. The hexane layer was concentrated on a rotary evaporation to yield the oxazine (IPA-OZ) as a yellow oil (approximately 370 g, 60% of theory). Note: Over a period of weeks, the oxazine will slowly convert to the hexahydropyrimidine as evidenced by its crystallization from the oil.

1. customA 2-liter, 3-neck round bottom flask equipped with a nitrogen blanket, addition funnel, mechanical stirrer
2. temperaturethe reactor contents cooled to 15 C with a cold water bath
3. additionAfter the addition
4. customthe cooling bath was removed
5. temperatureslowly warmed to 34° C. over 40 minutes
6. temperatureto warm the mixture to 70° C. for 5 hours
7. temperatureto cool back to room temperature overnight
8. additionHexane (750 mL) was then added
9. customthe water was azeotropically removed
10. customAs the last of the water was removed
11. customa white solid precipitated
12. customwas placed in the freezer overnight
13. customcrystallization
14. filtrationThe white, crystalline hexahydropyrimidine product was recovered via filtration, 245 g, 39.9% of theory
15. concentrationThe hexane layer was concentrated on a rotary evaporation

ORD record

ord-1f9ecf67774644a2b39f01ca49f000f5

Source dataset

uspto-grants-2008_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07319131B2