Dimethylformamide dimethyl acetal → HCID 86606785, compound

1G (296.15 g, 1.794 mol) was dissolved in THF (1.5 L) in a flask equipped with a mechanical stirrer and distillation head to give a thick slurry. DMF-DMA (263 mL, 1.1 eq) was added in one portion and slowly heated to gentle reflux. After 30 min at reflux, the reaction mixture became a homogeneous solution. The reaction was maintained at reflux for 1.5 h, and checked by HPLC and TLC (10:1 CH2Cl2/MeOH). At atmospheric pressure, 1150 mL THF was distilled out and replaced with 1500 mL heptane (Note that if the solution is not quite saturated, remaining THF should be removed by distillation). The remaining solution was cooled slowly to rt overnight with stirring, seeded at 68° C. Rapid crystallization was observed. The resulting slurry was cooled to 0° C., filtered and washed with heptanes (500 mL) and dried under vacuum at rt for 48 h. 384.6 g (97.4%) of 1H was isolated as a light tan crystalline solid. HPLC-MS using a neutral buffer ammonium acetate buffer system showed only a single peak, with the expected mass.

1. customequipped with a mechanical stirrer
2. distillationdistillation head
3. customto give a thick slurry
4. temperatureslowly heated to gentle reflux
5. temperatureAfter 30 min at reflux
6. temperatureThe reaction was maintained
7. temperatureat reflux for 1.5 h
8. distillationAt atmospheric pressure, 1150 mL THF was distilled out
9. customshould be removed by distillation)
10. customseeded at 68° C
11. customRapid crystallization
12. temperatureThe resulting slurry was cooled to 0° C.
13. filtrationfiltered
14. washwashed with heptanes (500 mL)
15. customdried under vacuum at rt for 48 h
16. custom384.6 g (97.4%) of 1H was isolated as a light tan crystalline solid

ORD record

ord-a8092d1943d34b55bc9bca64fbf03802

Source dataset

uspto-grants-2011_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08044242B2