US 6,982,329 B2 | ||
Process improvements in steroid chemistry | ||
David L. Burgoyne, Delta (Canada); Gueijun Ji, Richmond (Canada); Eugene W. Kelleher, Arlington, Mass. (US); Nicholas D. Paschalides, Marlborough, Mass. (US); Kishore Ramachandran, Burlington, Mass. (US); Yaping Shen, Port Coquitlam (Canada); and Yuanlin Zhou, Richmond (Canada) | ||
Assigned to Inflazyme Pharmaceuticals Ltd., Richmond (Canada) | ||
Filed on Dec. 22, 2003, as Appl. No. 10/744,857. | ||
Application 10/744857 is a division of application No. 10/154432, filed on May 22, 2002, granted, now 6,696,580. | ||
Claims priority of provisional application 60/293013, filed on May 22, 2001. | ||
Prior Publication US 2004/0138486 A1, Jul. 15, 2004 | ||
Int. Cl. C07J 21/00 (2006.01); C07J 11/00 (2006.01) |
U.S. Cl. 540—31 | 20 Claims |
1. A method comprising:
a) providing a compound of the formula: wherein:
![]() each of C1, C2, C4, C11, C12, C15 and C16 is independently substituted with
i) one of: ═O, ═C(R1)(R1), —C(R1)(R1)(C(R1)CR1))n— and —(O(C(R1)(R1))nO)— wherein n ranges from 1 to about 6; or
ii) two of the following, which are independently selected: —X, —R1 and —OR2;
C3 is substituted with hydrogen or -ZR3;
each of C8, C9 and C14 is independently substituted with one of —X, —R1 or —OR2;
C17 is substituted with two —OR2 groups or is a ketal;
R1 at each occurrence is independently selected from H and C1-30 organic moiety that may optionally contain at least one heteroatom selected from the group consisting of boron, halogen, nitrogen,
oxygen, silicon and sulfur, where two geminal R1 groups may together form a ring with the carbon atom to which they are both bonded;
R2 is H or a protecting group such that —OR2 is a protected hydroxyl group, where vicinal —OR2 groups may together form a cyclic structure which protects vicinal hydroxyl groups, and where geminal —OR2 groups may together form a cyclic structure which protects a carbonyl group, with the proviso that either or both of —OR2 at C6 and C7 represents a carbonyl or protected carbonyl group;
R3 is benzoyl or substituted benzoyl;
X represents fluoride, chloride, bromide and iodide; and
Z is selected from O, S and NR1;
b) contacting the compound with reagents comprising copper iodide and t-butyl hydroperoxide to provide a mixture; and
c) maintaining the mixture of step b) under oxidizing conditions to convert to compound to a product having a carbon skeleton
and an α,β-unsaturated ketone moiety as present in formula (4)
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