A highly selective method for 11β-OH protection of steroidal 11β, 17α-diols

Steroids

Volumn 73, Issue 5, 2008, Pages 574-577

  Glossop, Paul A ^a   Hoogenraad, Marcel ^a   Peakman, Torren M ^a   Roberts, Dannielle F ^a  

^a PFIZER GLOBAL RESEARCH AND DEVELOPMENT   (United Kingdom)

Author keywords

3 desilylation; Mono protection of diols; Reaction optimisation; Regioselective; Steroids

Indexed keywords

PREDNISOLONE; STEROID;

ARTICLE; CHEMICAL ANALYSIS; CHEMICAL STRUCTURE; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; SCREENING; SILYLATION; SUBSTITUTION REACTION;

STEROIDS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 40649099276     PISSN: 0039128X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.steroids.2008.01.016     Document Type: Article

References (11)

1. Bodor NS. United States Patent 4,996,335.
2. Ali A, Balkovec JM, Graham DW, Greenlee ML, Taylor GE. WO2004/066920.
3. 3 B: MeCN. Flow = 3 ml/min.
4. Typical procedure for TMS protection (5): Steroid (1) (22.1 g, 61.3 mmol) and imidazole (83.5 g, 1226 mmol, 20 equiv.) were dissolved in dry DMF (300 ml). Trimethylsilyl chloride (66.6 g, 613 mmol, 10 equiv.) was then added dropwise over 40 min before allowing the reaction mixture to stir at room temperature under nitrogen for 16 h. Quenched by addition of 50 ml MeOH and solvents evaporated under reduced pressure. 200 ml water was then added and mixture stirred for 30 min. The resulting white solid was filtered from solution and washed with 5× 25 ml water. Allowed to dry under reduced pressure in a vacuum oven at 50 °C for 16 h to give 30.9 g desired product (5) as an off white solid.
5. 4 and solvent evaporated under reduced pressure to give 22.24 g desired product (4) as a pale yellow solid.
6. 3): δ = 7.09 (C1, d, J = 10.1 Hz, 1H), 6.27 (C2, dd, J = 10.1, 1.8 Hz, 1H), 6.01 (C4, t, J ∼ 1.5 Hz, 1H), 4.48 (C11α, q, J ∼ 3.2 Hz, 1H), 3.77 (C21, s, 3H), 2.68 (C16β, ddd, J ∼ 2.8, 11.2, 14.4 Hz, 1H), 2.54 (C6β, ddd, J = 1.7, 4.7, 13.6 Hz, 1H), 2.32 (C6α, ddt, J = 1.8, 4.7, 13.6 Hz, 1H), 2.11 (C8β, m, 1H), 2.10 (C7β, m, 1H), 1.81 (C15α, dq, J ∼ 2.8, 9.5, 1H), 1.69 (C12β, dd, J = 13.8, 2.8 Hz, 1H), 1.69 (C16α, m, 1H), 1.64 (C12α, dd, J = 13.8, 3.5 Hz, 1H), 1.57 (C14α, dt, J ∼ 7.1, 10.6 Hz, 1H), 1.42 (C15β, dq, J ∼ 6.5, 11.9 Hz, 1H), 1.38 (C19, s, 3H), 1.13 (C7α, dq, J = 4.7, 13.6 Hz, 1H), 1.04 (C9α, dd, J = 10.9, 3.3 Hz, 1H), 0.94 (C18, s, 3H), 0.19 (s, 9H).
7. 3).
8. 5Si: C, 64.15; H, 8.49; Found: C, 64.09; H, 8.49 and C, 64.17; H, 8.54.
9. Huang-Minlon, Wilson E., Wendler N.L., and Tishler M. JACS 74 (1952) 5394-5396
10. Elks J., and Phillips G.H. J Chem Soc (1961) 4573-4576
11. Sandham D.A., Barker L., Beattie D., Beer D., Bidlake L., Bentley D., et al. Biorg Med Chem 12 (2004) 5213-5224