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

HRID 370414Notes

Reaction equation

HRID 370414 reaction equation
[CH3:1][C@@H:2]1[C@:19]([O:27]C(C)=O)(C(COC(C)=O)=O)[C@:18]2([CH3:31])[C@H:4]([C@H:5]3[C@:15](F)([C@@H:16](O)[CH2:17]2)[C@:14]2([CH3:34])[C:8](=[CH:9][C:10]([CH:12]=[CH:13]2)=[O:11])[C@@H:7]([F:35])[CH2:6]3)[CH2:3]1.F[C@@H]1C2[C@](C)(C=CC(=O)C=2)[C@@H]2[C@H]([C@H]3[C@@](C[C@@H]2O)(C)C(=O)CC3)C1.F[C@@H]1C2[C@](C)(C=CC(=O)C=2)C2[C@H]([C@H]3[C@@](CC=2)(C)C(=O)CC3)C1>>[F:35][C@@H:7]1[C:8]2[C@:14]([CH3:34])([CH:13]=[CH:12][C:10](=[O:11])[CH:9]=2)[C:15]2[C@H:5]([C@H:4]3[C@@:18]([CH2:17][CH:16]=2)([CH3:31])[C:19](=[O:27])[C:2](=[CH2:1])[CH2:3]3)[CH2:6]1

Participants

4

Reactant 3

HCID 71414Diflorasone diacetateHCID 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, U.S. Pat. No. 3,980,778) 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. Pat. No. 4,416,821 to produce 6α-fluoro-16-methyleneandrosta-1,4,9(11)-triene-3,17-dione 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. 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 difluorasone diacetate by the process of U.S. Pat. No. 3,980,778 (Examples 7 and 8).

Workup

  1. custom3,980,778) can be produced
  2. additionThe 16-methylene group is then added by the process of U.S

Sources & evidence

ORD record
ord-80e9fa9f2733480582b5b5db0258f590
Source dataset
uspto-grants-1985_07
Patent number
US04526720

Reaction notes

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