Formaldehyde → Benzaldehyde, 2-hydroxy-5-methyl-

Temperature

-10 °C

p-Cresol (100 g) in dry THF(100 ml) was added dropwise to a mechanically stirred, freshly prepared solution of ethyl magnesium bromide [magnesium (25.0 g) and bromoethane (75 ml)] in THF (500 ml) under nitrogen at a rate which maintained a slow reflux (about 30 mins). After 30 mins toluene (1.21) was added, followed by 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidone (125 ml), and paraformaldehyde (70 g). The mixture was then heated at reflux for 16 h. The mixture was concentrated by distillation and aqueous hydrochloric acid (2M, 600 ml) then added. Water (600 ml) was added and the mixture filtered through "hyflo". The organic phase was separated, dried, filtered and concentrated in vacuo to give a brown oil. The oil was steam distilled and the product extracted from the distillate with ether (1 liter). The organic extract was dried, filtered and concentrated in vacuo to give a pale yellow slurry which was cooled to -10° C., triturated with ether (precooled to -78° C., 100 ml), filtered off rapidly and washed with ether (precooled to -78° C.) to give the title compound as colourless needles, (131.4 g).

1. temperaturea slow reflux (about 30 mins)
2. temperatureThe mixture was then heated
3. temperatureat reflux for 16 h
4. concentrationThe mixture was concentrated by distillation and aqueous hydrochloric acid (2M, 600 ml)
5. additionthen added
6. additionWater (600 ml) was added
7. filtrationthe mixture filtered through "hyflo"
8. customThe organic phase was separated
9. customdried
10. filtrationfiltered
11. concentrationconcentrated in vacuo
12. customto give a brown oil
13. distillationdistilled
14. extractionthe product extracted from the distillate with ether (1 liter)
15. extractionThe organic extract
16. customwas dried
17. filtrationfiltered
18. concentrationconcentrated in vacuo
19. customto give a pale yellow slurry which
20. customtriturated with ether (precooled to -78° C., 100 ml)
21. filtrationfiltered off rapidly
22. washwashed with ether (precooled to -78° C.)

ORD record

ord-0b8566090d73449ba6c349f88b1a4a09

Source dataset

uspto-grants-1994_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05317023