3,4-dihydro-2H-pyran → 2-(4-Methoxy-3-nitrophenyl)-1-(3,4,5-trimethoxyphenyl)ethanone

Temperature

55 °C

A round-bottom flask equipped with thermometer, condenser and gas inlet was purged and maintained under nitrogen and charged with hydroxy-(3,4,5-trimethoxy-phenyl)-methyl]-phosphonic acid dimethyl ester (10 g, 32.6 mmol), 3,4-dihydro-2H-pyran (3.57 g, 42.4 mmol), toluene (100 mL) and p-toluenesolfonic acid hydrate (62.1 mg, 0.01 eq). Resulted solution was stirred at 55° C. for 1.5 hours. TLC (EtOAc) showed full conversion of starting material into a less polar compound. Reaction mixture was cooled to −10° C. and a solution of sodium bis(trimethylsilyl)amide in THF (1M, 33.3 mL) was added drop-wise, followed by a solution of 4-methoxy-3-nitrobenzaldehyde (5.91 g, 32.6 mmol) in THF (20 mL). Reaction mixture was stirred at 0° C. for 1 hour before allowed to warm to room temperature. TLC (Hx:EtOAc, 2:1) showed formation of Z/E isomers of 2-[2-(4-methoxy-3-nitro-phenyl)-1-(3,4,5-trimethoxy-phenyl)-vinyloxy]-tetrahydro-pyran and traces of starting materials remaining. Reaction was quenched with water (140 mL), diluted with EtOAc (60 mL) and transferred into separatory funnel. Organic layer was separated, washed with water (2×50 mL), brine, and concentrated. A residue was dissolved in methanol (100 mL) with energetic mechanical stirring, and 1M aqueous solution of HCl (10 mL) was added. Precipitation of product started soon, and a resulted suspension was stirred for 1 hour. Solid was filtered out, washed with methanol (50 mL), then with water (3×30 mL) and dried on filter followed by vacuum-drying at 60° C. until constant weight. Crude deoxybenzoin 2, 6.81 g (58%) showed LC purity of ≧97% and was used in the next step without further purification.

1. customA round-bottom flask equipped with thermometer, condenser and gas inlet
2. customwas purged
3. temperaturemaintained under nitrogen
4. customReaction mixture
5. temperaturewas cooled to −10° C.
6. customReaction mixture
7. stirringwas stirred at 0° C. for 1 hour
8. temperatureto warm to room temperature
9. customReaction
10. customwas quenched with water (140 mL)
11. additiondiluted with EtOAc (60 mL)
12. customtransferred into separatory funnel
13. customOrganic layer was separated
14. washwashed with water (2×50 mL), brine
15. concentrationconcentrated
16. dissolutionA residue was dissolved in methanol (100 mL) with energetic mechanical stirring, and 1M aqueous solution of HCl (10 mL)
17. additionwas added
18. customPrecipitation of product
19. stirringa resulted suspension was stirred for 1 hour
20. filtrationSolid was filtered out
21. washwashed with methanol (50 mL)
22. dry with materialwith water (3×30 mL) and dried
23. filtrationon filter
24. customby vacuum-drying at 60° C. until constant weight
25. customwas used in the next step without further purification

ORD record

ord-a5e6e13cc85b4f06907aba507ed966ea

Source dataset

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08598366B2