Synthesis of 1.alpha.,25-dihydroxyergocalciferol

• US 4,508,651 A
• Filed: 03/21/1983
• Issued: 04/02/1985
• Est. Priority Date: 03/21/1983
• Status: Expired due to Fees

• Current Assignee: Hoffmann-La Roche Incorporated (Roche Holding AG)
• Original Assignee: Hoffmann-La Roche Incorporated (Roche Holding AG)
• Inventors: Uskokovic, Milan R., Baggiolini, Enrico G., Batcho, Andrew D., Boris, Alfred
• Primary Examiner(s): Roberts, Elbert L.
• Application Number:
  US06/477,059
• Time in Patent Office: 743 Days
• Field of Search: 260/397.2
• US Class Current: 552/653
• CPC Class Codes: A61P 3/02 Nutrients, e.g. vitamins, minerals
• CPC Class Codes: C07C 35/32 the condensed ring system being a (4.3.0) system, e.g. indenols
• CPC Class Codes: C07C 45/305 with halogenochromate reagents, e.g. pyridinium chlorochromate
• CPC Class Codes: C07C 45/44 by reduction and hydrolysis of nitriles
• CPC Class Codes: C07C 47/192 containing rings
• CPC Class Codes: C07C 49/743 having unsaturation outside the rings, e.g. humulones, lupulones
• CPC Class Codes: C07D 261/02 not condensed with other rings
• CPC Class Codes: C07F 7/1804 Compounds having Si-O-C linkages Si-O-acyl linkages C07F7/1896

Abstract

The invention is directed to a process and intermediates for the preparation of 1α,25-dihydroxyergocalciferol as well as substantially pure and crystalline 1α,25-dihydroxyergocolciferol. The end-product 1α,25-dihydroxyergocalciferol is useful in the treatment of disease states which are characterized by insufficient amounts of 1α,25-dihydroxycholecalciferol.

Claims

1. A process of the preparation of 1α

,25-dihydroxyergocalciferol of the formula ##STR22## which comprises the steps of (a) reacting a compound of the formula ##STR23## wherein R₁ is lower alkyl, aryl, or ar-lower alkyl, with a compound of the formula ##STR24## wherein R₁ is as previously described to yield a corresponding compound of the formula ##STR25## wherein R₁ as previously described, and (b) removing the protecting groups from a compound of formula IV, whereby there is obtained the compound of formula I.

2. A process in accordance with claim 1, wherein R₁ is lower alkyl.

3. A process in accordance with claim 2, wherein the removal of the protecting groups is effected by treating compound of the formula IV with tetrabutylammonium fluoride in tetrahydrofuran.