6alpha-Fluoroandrost-1,4,9(11)-triene-3,17-dione → 6alpha-Fluoro-16-methyleneandrosta-1,4,9(11)-triene-3,17-dione

HRID 1285306Notes

Reaction equation

HRID 1285306 reaction equation
[F:1][C@@H:2]1[C:19]2[C@:14]([CH3:21])([CH:15]=[CH:16][C:17](=[O:20])[CH:18]=2)[C@@H:13]2[C@H:4]([C@H:5]3[C@@:9]([CH2:11][C@@H:12]2O)([CH3:10])[C:8](=[O:23])[CH2:7][CH2:6]3)[CH2:3]1.F[C@@H:25]1C2[C@](C)(C=CC(=O)C=2)C2[C@H]([C@H]3[C@@](CC=2)(C)C(=O)CC3)C1>>[F:1][C@@H:2]1[C:19]2[C@:14]([CH3:21])([CH:15]=[CH:16][C:17](=[O:20])[CH:18]=2)[C:13]2[C@H:4]([C@H:5]3[C@@:9]([CH2:11][CH:12]=2)([CH3:10])[C:8](=[O:23])[C:7](=[CH2:25])[CH2:6]3)[CH2:3]1

Participants

3

Reactant 2

HCID 541080436alpha-Fluoroandrost-1,4,9(11)-triene-3,17-dioneHCID 70407082HCID 70407082, compound

Product 1

HCID 572010876alpha-Fluoro-16-methyleneandrosta-1,4,9(11)-triene-3,17-dione

Procedure

Likewise diflorasone diacetate (6α,9α-difluoro-11β,17α,21-trihydroxy-16β-methylpregna-1,4-diene-3,20-dione 17,21-diacetate) can be produced using the process of the present invention. First, 6α-fluoro-11β-hydroxyandrosta-1,4-diene-3,17-dione (U.S. Pat. No. 2,867,630) is dehydrated to 6α-fluoroandrost-1,4,9(11)-triene-3,17-dione by means well known to those skilled in the art, see Steroid Reactions, C. Djerassi, Holden-Day, San Francisco, 1963 p. 238 & 239. The 16-methylene group is then added by the process of U.S. patent application Ser. No. 349,490 to produce 6α-fluoro-16-methyleneandrosta-1,4,9(11)-triene-3,17-dione (IIIB) which is converted by the process of the present invention to 6α-fluoro-17α-hydroxy-16-methylenepregna-1,4,9(11)-triene-3,20-dione (VIIB). The 21-hydroxy function of the corticoids is next introduced as described above followed by transformation of the 16-methylene group to a 16β-methyl group also described above to give 6α-fluoro-17α,21-dihydroxy-16β-methylpregna- 1,4,9(11)-triene-3,20-dione 21-acetate which is acylated according to the procedure described in U.S. Pat. No. 4,154,748 (Examples 6 and 7) to produce 6α-fluoro-17α,21-dihydroxy-16β-methylpregna-1,4,9(11)-triene-3,20-dione 17,21-diacetate (U.S. Pat. No. 3,980,778, Example 6). 6α-fluoro-17α,21-dihydroxy-16β-methylpregna-1,4,9(11)-triene-3,20-dione-17,21-diacetate is then converted to diflorasone diacetate by the process of U.S. Pat. No. 3,980,778 (Examples 7 and 8).

Workup

  1. additionThe 16-methylene group is then added by the process of U.S

Sources & evidence

ORD record
ord-1f1eedc3d0d24de6a26a5251214e0fcf
Source dataset
uspto-grants-1986_01
Patent number
US04567001

Reaction notes

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