Crystallization of (20R) and (20S) analogs of 2-methylene-19-nor-24-dimethyl-1α,25-dihydroxyvitamin D

1. A compound having the formula

in crystalline form, wherein the methyl group attached to carbon 20 may be in its R or S orientation.

2. (20S)-2-methylene-19-nor-22-dimethyl-1α,25-dihydroxyvitamin D 3 in crystalline form.

3. A crystalline form of (20S)-2-methylene-19-nor-22-dimethyl-1α,25-dihydroxyvitamin D 3 having molecular packing arrangement defined by space group P2(1) and unit cell dimensions a=7.57 Å b=14.79 Å c=14.48 Å α=90°, β=102.2° and γ=90°.

4. A three dimensional structure for (20S)-2-methylene-19-nor-22-dimethyl-1α,25-dihydroxyvitamin D 3 as defined by the molecular packing arrangement set forth in claim 3 .

5. A method of purifying (20S)-2-methylene-19-nor-22-dimethyl-1α,25-dihydroxyvitamin D 3 , comprising the steps of:

(a) preparing a solvent comprising diethyl ether;

(b) dissolving a product containing (20S)-2-methylene-19-nor-22-dimethyl-1α,25-dihydroxyvitamin D 3 to be purified in said solvent;

(c) cooling said solvent and dissolved product below ambient temperature for a sufficient amount of time to form a precipitate of (20S)-2-methylene-19-nor-22-dimethyl-1α,25-dihydroxyvitamin D 3 crystals; and

(d) separating the (20S)-2-methylene-19-nor-22-dimethyl-1α,25-dihydroxyvitamin D 3 crystals from the solvent.

6. The method of claim 5 including the further step of allowing said solvent and dissolved product to cool to ambient temperature prior to cooling below ambient temperature.

7. The method of claim 5 wherein said solvent comprises 100% diethyl ether, by volume.

8. The method of claim 5 wherein the step of separating comprises filtering the solvent and precipitate to obtain the crystals.

9. The method of claim 5 including a further step (e) comprising repeating steps (a) through (d) using the recovered crystals from step (d) as the product of step (b).

10. (20R)-2-methylene-19-nor-22-dimethyl-1α,25-dihydroxyvitamin D 3 in crystalline form.

11. A crystalline form of (20R)-2-methylene-19-nor-22-dimethyl-1α,25-dihydroxyvitamin D 3 having molecular packing arrangement defined by space group C2 and unit cell dimensions a=27.33 Å b=6.68 Å c=19.22 Å α=90°, β=113.57° and γ=90°.

12. A three dimensional structure for (20R)-2-methylene-19-nor-22-dimethyl-1α,25-dihydroxyvitamin D 3 as defined by the molecular packing arrangement set forth in claim 11 .

13. A method of purifying (20R)-2-methylene-19-nor-22-dimethyl-1α,25-dihydroxyvitamin D 3 , comprising the steps of:

(a) preparing a solvent comprising hexane;

(b) adding a product containing (20R)-2-methylene-19-nor-22-dimethyl-1α,25-dihydroxyvitamin D 3 to be purified to said hexane to form a suspension of the product in the hexane;

(c) adding 2-propanol dropwise to the suspension to form a mixture of the product in the hexane and 2-propanol;

(d) heating the mixture to dissolve the product containing (20R)-2-methylene-19-nor-22-dimethyl-1α,25-dihydroxyvitamin D 3 to be purified in said mixture;

(e) cooling said mixture and dissolved product below ambient temperature for a sufficient amount of time to form a precipitate of (20R)-2-methylene-19-nor-22-dimethyl-1α,25-dihydroxyvitamin D 3 crystals; and

(f) separating the (20R)-2-methylene-19-nor-22-dimethyl-1α,25-dihydroxyvitamin D 3 crystals from the mixture.

14. The method of claim 13 including the further step of allowing said mixture and dissolved product to cool to ambient temperature prior to cooling below ambient temperature.

15. The method of claim 13 wherein the step of separating comprises filtering the mixture and precipitate to obtain the crystals.

16. The method of claim 13 including a further step (g) comprising repeating steps (a) through (f) using the recovered crystals from step (f) as the product of step (b).

17. The method of claim 13 wherein said mixture comprises about 15% 2-propanol and about 85% hexane, by volume.