Uses
Tetrahydro-2H-pyran-3-ol is a 3-substituted tetrahydropyran used in the preparation of herbicides as well as pyrazolothiazole compounds as CRF1 (corticotropin-releasing factor type 1) receptor antagonists.
Synthesis Reference(s)
The Journal of Organic Chemistry, 35, p. 2282, 1970
DOI: 10.1021/jo00832a038
Synthesis
Under nitrogen protection, 3,4-dihydro-2H-pyran (840 g, 10 mol) was dissolved in 4000 g of anhydrous tetrahydrofuran and cooled to 0 °C. A 1M borane tetrahydrofuran complex solution (6000 mL, 6 mol) was added dropwise at 0 °C and stirring was maintained. Subsequently, the reaction mixture was slowly cooled from room temperature to 0 °C over a period of 2 h and 3000 g of 20% NaOH aqueous solution was added dropwise. After the dropwise addition, hydrogen peroxide (1700 g, 15 mol) was added dropwise, the reaction temperature was controlled at 48 °C and stirred at room temperature for 9 hours. Upon completion of the reaction, saturated Na2S2O3 solution was added to quench the hydrogen peroxide, followed by concentration. The aqueous phase was extracted three times with 2000 g of dichloromethane, and the organic phases were combined, dried and concentrated. Finally, distillation was carried out under reduced pressure by pumping and the fractions were collected at an oil bath temperature of 140 °C and a fraction temperature of 100 °C to give 550 g of a colorless oily liquid with a purity of 98% and a yield of 52.8%.
References
[1] Journal of the Chemical Society, Chemical Communications, 1987, p. 1857 - 1859
[2] Patent: CN107382928, 2017, A. Location in patent: Paragraph 0007; 0010; 0013
[3] Patent: CN104650049, 2018, B. Location in patent: Paragraph 0599; 0600
[4] Canadian Journal of Chemistry, 1983, vol. 61, p. 1924 - 1932
[5] Liebigs Annalen der Chemie, 1983, # 11, p. 1950 - 1958
