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Synlett 2005(5): 0817-0818  
DOI: 10.1055/s-2005-863733
LETTER
© Georg Thieme Verlag Stuttgart · New York

A Facile One-Pot Synthesis of 7-Triethylsilylbaccatin III

Erkan Baloglu*, Michael L. Miller, Emily E. Cavanagh, Tracy P. Marien, Elizabeth E. Roller, Ravi V. J. Chari
ImmunoGen Inc., 128 Sidney Street, Cambridge, MA 02139, USA
Fax: +1(617)9952510; e-Mail: erkan.baloglu@immunogen.com;
Further Information

Publication History

Received 23 November 2004
Publication Date:
09 March 2005 (online)

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Abstrac

A one-pot synthesis of 7-triethylsilylbaccatin III has been delineated. The reaction can easily be extended for the preparation of analogs of baccatin III.

Key words

taxol - taxotere - baccatin - paclitaxel - docetaxel

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Experimental Procedure for 7-Triethylsilylbaccatin III (4).
To a stirred solution of 10-deacetylbaccatin III (3, 2.72 g, 5 mmol) in pyridine (13.5 mL) was added imidazole (2.04 g, 30 mmol) and chlorotriethylsilane (1.6 mL, 10 mmol) at r.t. The reaction mixture was stirred for 5 min where acetic anhydride (9.5 mL, 100 mmol) was introduced dropwise. The reaction mixture was stirred for additional 4-5 h and when the completion of the reaction is confirmed by MS the reaction was diluted with EtOAc, washed with aq sat. NaHCO3, H2O and brine. The organic phase was dried over Na2SO4 and the concentrated crude product was purified by column chromatography (EtOAc-hexane, 60:40) to give the desired product (82% yield for two steps).
Analytical data: 1H NMR (CDCl3): δ = 8.08 (d, 2 H), 7.58 (t, 1 H), 7.45 (t, 2 H), 6.44 (s, 1 H), 5.61 (d, 1 H), 4.94 (d, 1 H), 4.80 (m, 1 H), 4.48 (m, 1 H), 4.28 (d, 1 H), 4.11 (d, 1 H), 3.86 (d, 1 H), 2.49 (m, 1 H), 2.23 (s, 3 H), 2.22 (t, 3 H), 2.10 (s, 6 H), 1.82 (m, 1 H), 1.68 (d, 1 H), 1.66 (s, 3 H), 1.17 (s, 3 H), 1.01 (s, 3 H), 0.89 (t, 9 H), 0.49-0.63 (m, 6 H). 13C NMR (CDCl3): δ = 202.57, 171.01, 169.67, 167.39, 144.38, 133.91, 132.96, 130.40, 129.74, 128.90, 84.54, 81.15, 79.03, 76.83, 76.13, 75.08, 72.67, 68.21, 58.97, 47.58, 43.09, 38.66, 37.56, 27.11, 22.96, 21.24, 20.42, 15.24, 10.26, 7.05, 5.60. LRMS [MNa]+: m/z calcd for C37H52O11SiNa: 723.32; found: 723.20.