A Simple Method for 6-Methylenation of 3-Oxo-Δ⁴-steroids

6-Methylideneandrost-4-ene-3,17-dione

“…For the synthesis of the title compound, see: Annen et al (1982). For exemestane aromatase inhibitor potency, see: Furr (2006).…”

“…6-Methylenandrost-4-ene-3,17-dione was prepared according to a described procedure (Annen et al, 1982) as follows. A suspension of anhydrous sodium acetate (1.0 g, 12.19 mmol) in dry chloroform (30.0 cm 3 ) containing formaldehyde dimethyl acetal (30.0 cm 3 , 340.0 mmol) and phosphoryl choride (1.9 cm 3 , 20.0 mmol) was heated at reflux for 1 h. Androstenedione (773.5 mg, 2.70 mmol) was then added and the mixture was supplemented dropwise with phosphoryl choride (1.9 cm 3 , 20.0 mmol) over a period of 3 h 30 min.…”

Features of hydrocortisone C6-alkylation

“…Recrystallization from CH 2 Cl 2 produced VII (2.18 g), 96% yield, mp 220 -223°C (lit. [13] mp 224 -226°C).…”

“…However, the 6-methylene derivative was produced in 50% yield upon methylenation of the 21-acetate of I with a trifluoroacetate-protected 11â-hydroxyl and an unprotected 17a-hydroxyl; in only 18% yield with unprotected 11b-and 17a-hydroxyls [13]. This can be explained by side reactions involving the unprotected groups.…”

Dimethoxymethane

“…The reaction can also be carried out using diethoxyethane and other formaldehyde acetals. Of these, diethoxymethane and dimethoxymethane yield superior results 25. …”