Tetrahydrofuran → HCID 12782002, compound

Temperature

0 °C

A solution of (S)-phenylglycinol (15 g) and p-anisaldehyde (16.4 g) in methyl tert-butyl ether (150 mL) was heated to reflux, with a Dean-Stark trap attached, for about 3 hours. Tetrahydrofuran (60 mL) was added and the mixture cooled to 0° C. To this was added a solution of m-chloroperoxybenzoic acid (29.8 g) in methyl tert-butyl ether (80 mL), maintaining the temperature below 5° C. The mixture was stirred at 0° C. for about 3 hours. Then the reaction mixture was washed with 10% aqueous potassium carbonate (3×75 mL). The resulting organic layer was concentrated to a smaller volume. To this was added a solution of hydroxylamine hydrochloride (15.3 g) in methanol (19 mL) and water (27 mL), and the reaction was stirred at room temperature for about 3 hours. Heptane (30 mL) and water (30 mL) were added. The layers were separated, and the aqueous layer was washed with methyl tert-butyl ether (3×30 mL). The methanol was removed by vacuum distillation, and then methyl tert-butyl ether (75 ml) was added. After adjusting the pH to 7 with solid potassium carbonate, sodium chloride was added and the layers separated. The aqueous layer was further extracted with methyl tert-butyl ether (2×75 mL). The combined methyl tert-butyl ether extracts were filtered, concentrated to a small volume, and then heptane (70 mL) was added. The resulting slurry was stirred at room temperature for about 1 hour and then cooled to 0° C. After stirring for 1 hour, the mixture is filtered and the wetcake washed with heptane (20 mL). The wetcake was then dissolved in dichloromethane (100 mL) for use in the next step. 1H NMR (400 MHz, CDCl3) δ 3.83–3.91 (2H, m), 4.12 (1H, dd, J=6.9, 4.8 Hz), 4.84 (3H, br s), 7.27–7.36 (5H, m). 13C NMR (100 MHz, CDCl3) δ 63.8, 67.7, 127.5, 127.9, 128.4, 137.5.

1. temperatureto reflux, with a Dean-Stark trap
2. temperaturemaintaining the temperature below 5° C
3. washThen the reaction mixture was washed with 10% aqueous potassium carbonate (3×75 mL)
4. concentrationThe resulting organic layer was concentrated to a smaller volume
5. additionTo this was added a solution of hydroxylamine hydrochloride (15.3 g) in methanol (19 mL) and water (27 mL)
6. stirringthe reaction was stirred at room temperature for about 3 hours
7. additionHeptane (30 mL) and water (30 mL) were added
8. customThe layers were separated
9. washthe aqueous layer was washed with methyl tert-butyl ether (3×30 mL)
10. customThe methanol was removed by vacuum distillation
11. additionmethyl tert-butyl ether (75 ml) was added
12. additionwas added
13. customthe layers separated
14. extractionThe aqueous layer was further extracted with methyl tert-butyl ether (2×75 mL)
15. filtrationThe combined methyl tert-butyl ether extracts were filtered
16. concentrationconcentrated to a small volume
17. additionheptane (70 mL) was added
18. stirringThe resulting slurry was stirred at room temperature for about 1 hour
19. temperaturecooled to 0° C
20. stirringAfter stirring for 1 hour
21. filtrationthe mixture is filtered
22. washthe wetcake washed with heptane (20 mL)
23. dissolutionThe wetcake was then dissolved in dichloromethane (100 mL) for use in the next step

ORD record

ord-c434cfb290cc402e8e3752f577e899ca

Source dataset

uspto-grants-2008_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07354937B2