Key intermediate for the preparation of Stilbenes, solid forms of Pterostilbene, and methods for making the same

1. A compound of formula 1

wherein R 1 and R 2 independently represent hydrogen, lower alkyl or aralkyl.

2. A process for the preparation of the compound of formula 1, comprising the step of condensing 3,5-Dialkylbenzyl phosphonates with 4′-O-tetrahydropyranyl benzaldehyde in presence of a base.

3. The process as claimed in claim 2 , wherein the base is sodium hydride.

4. A process for the preparation of stilbene of formula 2,

wherein R 1 and R 2 independently represent hydrogen, lower alkyl or aralkyl, comprising the steps of:

condensing 4′-O-tetrahydropyranyl benzaldehyde with a compound of formula 3

to obtain a compound of formula 1

and

deprotecting the compound of formula 1 to obtain the stilbene of formula 2.

5. The process as claimed in claim 4 , wherein each of R1 and R2 is methyl, and the stilbene is Pterostilbene.

6. The process as claimed in claim 4 , wherein each of R1 and R2 is hydrogen, and the stilbene is resveratrol.

7. Form I Pterostilbene having x-ray powder diffraction peaks, when measured with Cu—Kα radiation, at about 16.7 and 8.3°2θ, and a melting point of about 94-96° C.

8. Form II Pterostilbene having x-ray powder diffraction peaks, when measured with Cu—Kα radiation, at about 5.3, 9.6, and 10.5°2θ.

9. Form III Pterostilbene having x-ray powder diffraction peaks, when measured with Cu—Kα radiation, at about 11.3, 13.8, 14.1, 14.9, and 15.5°2θ.

10. Form IV Pterostilbene having x-ray powder diffraction peaks, when measured with Cu—Kα radiation, at about 8.4, 10.0, 12.0 and 15.3°2θ.

11. Form V Pterostilbene having x-ray powder diffraction peaks, when measured with Cu—K α radiation, at about 5.2, 8.1, 8.9, 10.4, 12.1, or 14.2°2θ.

12. X-ray amorphous Pterostilbene having substantially the same x-ray powder diffraction pattern of FIG. 9 .

13. Pterostilbene Form I of claim 7 , further having one or more x-ray powder diffraction peaks at about 12.5 or 15.8°2θ.

14. Pterostilbene Form I of claim 7 , having substantially the same x-ray powder diffraction pattern of FIG. 2 when measured with Cu—K α radiation.

15. Pterostilbene of Form I of claim 7 , having substantially the same Raman spectrum of FIG. 12 .

16. Pterostilbene Form II of claim 8 , further having one or more x-ray powder diffraction peaks at about 12.6 or 15.7°2θ.

17. Pterostilbene Form II of claim 8 , having substantially the same x-ray powder diffraction pattern of FIG. 3 when measured with Cu—K α radiation.

18. Pterostilbene Form II of claim 8 , having substantially the same Raman spectrum of FIG. 13 .

19. Pterostilbene Form III of claim 9 , having substantially the same x-ray powder diffraction pattern of FIG. 5 when measured with Cu—K α radiation.

20. Pterostilbene Form III of claim 9 , having substantially the same Raman spectrum as FIG. 14 .

21. Pterostilbene Form IV of claim 10 , having substantially the same x-ray powder diffraction pattern of FIG. 6 when measured with when measured with Cu—K α radiation.

22. Pterostilbene Form IV of claim 10 , having substantially the same Raman spectrum of FIG. 15 .

23. Pterostilbene Form V of claim 11 , having substantially the same x-ray powder diffraction pattern of FIG. 7 when measured with Cu—K α radiation.

24. Pterostilbene Form V of claim 11 , having substantially the same Raman spectrum of FIG. 16 .

25. A t-butanol solvate of Pterostilbene having substantially the same x-ray powder diffraction pattern as FIG. 8 .

26. Pterostilbene Form I of claim 7 , having Raman peaks at about 195, 865, and 1358 cm −1 .

27. Pterostilbene Form I of claim 7 , having Raman peaks at about 865 and 1358 cm −1 .

28. Pterostilbene Form II of claim 8 , having Raman peaks at about 960, 1442, and 1587 cm −1 .

29. Pterostilbene Form III of claim 9 , having Raman peaks at about 958, 1187, and 1439 cm −1 .

30. Pterostilbene Form IV of claim 10 , having Raman peaks at about 862 cm −1 and 1320 cm −1 and a melting point of about 76° C.

31. Pterostilbene Form IV of claim 10 , having Raman peaks at about 200, 862, and 1320 cm −1 .

32. Pterostilbene Form IV of claim 31 , further having a melting point of about 76° C.

33. Pterostilbene Form V of claim 11 , having Raman peaks at about 867, 962, and 1444 cm −1 .

34. A process for preparing the Pterostilbene Form I of claim 7 , comprising the steps of:

treating a solution of (2-4-[(E)-2-(3,5-dimethoxyphenyl)-1-ethenyl]phenoxy tetra hydro-2H-pyran) with pyridinium p-toluenesulfonate in methanol;

removing the methanol to obtain a solid;

dissolving the solid in ethyl acetate; and

precipitating Pterostilbene Form I with acetone.

35. A process for preparing the Pterostilbene Form II of claim 8 , comprising the steps of:

dissolving a Pterostilbene Form I in trifluoroethanol, wherein the Pterostilbene Form I has x-ray powder diffraction peaks, when measured with Cu—Kα radiation, at about 16.7 and 8.3°2θ, and a melting point of about 94-96° C.; and

cooling to precipitate Pterostilbene Form II.

36. A process for preparing the Pterostilbene Form II of claim 8 , comprising the steps of:

dissolving solid Pterostilbene in acetonitrile; and

evaporating the acetonitrile to precipitate Pterostilbene Form II.

37. A process for preparing the Pterostilbene Form III of claim 9 , comprising the steps of

dissolving solid Pterostilbene in methanol; and

evaporating the methanol to precipitate Pterostilbene Form III.

38. A process for preparing the Pterostilbene Form IV of claim 10 , comprising the steps of:

dissolving solid Pterostilbene in methanol; and

slowly evaporating the methanol to precipitate Pterostilbene Form IV.

39. A process for preparing the Pterostilbene Form V of claim 11 , comprising the steps of exposing amorphous Pterostilbene at less than 10% relative humidity and room temperature to form Pterostilbene Form V.