Crystallization of 1α-hydroxy-2-methylene-18,19-dinor-homopregnacalciferol
A method of purifying 1α-hydroxy-2-methylene-18,19-dinor-homopregnacalciferol to obtain 1α-hydroxy-2-methylene-18,19-dinor-homopregnacalciferol in crystalline form using precipitation with hexane from ethyl acetate. A method of preparing 1α-hydroxy-2-methylene-18,19-dinor-homopregnacalciferol crystals acceptable for X-ray experiment using precipitation with hexane from benzene by diffusive exchange of the solvents is also described.
1. 1α-hydroxy-2-methylene-18,19-dinor-homopregnacalciferol in crystalline form.
2. The crystalline form of 1α-hydroxy-2-methylene-18,19-dinor-homopregnacalciferol having molecular packing arrangement defined by space group P2 and unit cell dimensions a=4.8 Å, b=22.9 Å, c=36.1 Å, α=90°, β=90° and γ=90°.
3. A three dimensional structure for 1α-hydroxy-2-methylene-18,19-dinor-homopregnacalciferol as defined by the molecular packing arrangement set forth in claim 2 .
4. A method of purifying 1α-hydroxy-2-methylene-18,19-dinor-homopregnacalciferol, comprising the steps of:
(a) dissolving a product containing 1α-hydroxy-2-methylene-18,19-dinor-homopregnacalciferol to be purified in a solvent comprising ethyl acetate;
(b) adding hexane to said solvent and dissolved product to form a mixture;
(c) cooling said mixture containing said dissolved product below ambient temperature for a sufficient amount of time to form a precipitate of 1α-hydroxy-2-methylene-18,19-dinor-homopregnacalciferol crystals; and
(d) separating the 1α-hydroxy-2-methylene-18,19-dinor-homopregnacalciferol crystals from the mixture.
5. The method of claim 4 wherein the step of separating comprises filtering the mixture and precipitate to obtain the crystals.
6. The method of claim 4 including a further step (d) comprising repeating steps (a) through (c) using the recovered crystals from step (c) as the product of step (a).
7. The method of claim 4 wherein a ratio of ethyl acetate and hexane is about 1:99, by volume.
8. A method of preparing 1α-hydroxy-2-methylene-18,19-dinor-homopregnacalciferol crystals by diffusive exchange of solvents, comprising the steps of:
(a) dissolving a product containing 1α-hydroxy-2-methylene-18,19-dinor-homopregnacalciferol in a first solvent comprising benzene;
(b) providing a second solvent comprising hexane;
(c) allowing said first solvent with dissolved product and said second solvent to diffuse together for a sufficient amount of time to form a precipitate of 1α-hydroxy-2-methylene-18,19-dinor-homopregnacalciferol crystals; and
(d) recovering the 1α-hydroxy-2-methylene-18,19-dinor-homopregnacalciferol crystals.
9. The method of claim 8 wherein a ratio of benzene and hexane is about 13:87, by volume.
10. The method of claim 8 wherein the step of recovering comprises filtering to obtain the crystals.
11. The method of claim 8 wherein the step of allowing said first solvent with dissolved product and said second solvent to diffuse together takes place in a closed system purged with argon.
12. The method of claim 8 wherein the step of allowing said first solvent with dissolved product and said second solvent to diffuse together takes place at room temperature.