Crystallization of (20R)-2-methylene-19-nor-24-difluoro-1α,25-dihydroxyvitamin D3
Disclosed are methods of purifying the compound (20R)-2-methylene-19-nor-24-difluoro-1α,25-dihydroxyvitamin D 3 to obtain the compound in crystalline form. The methods typically include the steps of dissolving a product containing the compound in a solvent comprising hexane and 2-propanol, cooling the solvent and dissolved product below ambient temperature for a sufficient amount of time to form a precipitate of crystals, and recovering the crystals.
1. A compound having the formula:
in crystalline form, and named (20R)-2-methylene-19-nor-24-difluoro-1α,25-dihydroxyvitamin D 3 .
2. A crystalline form of (20R)-2-methylene-19-nor-24-difluoro-1α,25-dihydroxyvitamin D 3 having molecular packing arrangement defined by space group C2 and unit cell dimensions a=23.84Å b=6.27Å c=20.71 Å α=90°, β=126.52° and γ=90°.
3. A three dimensional structure for (20R)-2-methylene-19-nor-24-difluoro-1α,25-dihydroxyvitamin D 3 as defined by the molecular packing arrangement set forth in claim 2 .
4. A method of purifying (20R)-2-methylene-19-nor-24-difluoro-1α25-dihydroxyvitamin D 3 , comprising the steps of:
(a) preparing a solvent comprising hexane;
(b) adding a product containing (20R)-2-methylene-19-nor-24-difluoro-1α,25-dihydroxyvitamin D 3 to he 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-24-difluoro-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 (2W)-2-methylene-19-nor-24-difluoro-1α,25-dihydroxyvitamin D 3 crystals; and
(f) separating the (20R)-2-methylene-19-nor-24-difluoro-1α,25-dihydroxyvitamin D 3 crystals from the solvent.
5. The method of claim 4 including the further step of allowing said mixture and dissolved product to cool to ambient temperature prior to cooling below ambient temperature.
6. The method of claim 4 wherein the step of separating comprises filtering the mixture and precipitate to obtain the crystals.
7. The method of claim 4 including a further step (g) comprising repeating steps (a) through (f) using the recovered crystals from step (f) as the product of step (b).
8. The method of claim 4 wherein said mixture comprises about 15% 2-propanol and about 85% hexane, by volume.