Synthesis of 3-carboxy-20-keto steroid, SB 209963, a 5α-reductase inhibitor, by palladium-catalyzed hydroxycarbonylation

Tetrahedron Letters

Volumn 40, Issue 16, 1999, Pages 3123-3124

  Yu, Marvin S ^a   Baine, Neil H ^a  

^a GLAXOSMITHKLINE   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

3 CARBOXY 20 KETO STEROID; HALIDE; PALLADIUM; SB 209963; STEROID 5ALPHA REDUCTASE INHIBITOR; UNCLASSIFIED DRUG;

ALOPECIA; ARTICLE; CARBOXYLATION; CATALYSIS; CATALYST; CHEMICAL REACTION; ENZYME ACTIVITY; ENZYME INHIBITION; HYDROLYSIS; PROSTATE HYPERTROPHY; SYNTHESIS;

EID: 0033574589     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(99)00456-6     Document Type: Article

References (11)

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3. Yamashita, D.S.; Holt, D.A.; Oh, H.-J.; Shah, D.; Yen, H.-K.: Brandt, M.; Levy, M.A. Bioorg. Med. Chem. 1996, 4, 1481.
4. Holt, D.A.; Levy, M.A.; Ladd, D.L.; Oh, H.-J.; Erb, J.M.; Heaslip, J.I.; Brandt, M.; Metcalf, B.W. J. Med. Chem. 1990, 33, 937.
5. Weinreb, S.M.; Nahm, S. Tetrahedron Lett. 1981, 23, 3815.
6. a) Bhattachyarya, A.: Williams, J.M.; Amato, J.S.; Dolling, U.-H.; Grabowski, E.J.J. Syn. Commun. 1990, 20, 2683.
7. b) Williams, J.M.; Jobson, R.B.; Yasuda, N.; Marchesini, G.; Dolling, U.-H.; Grabowski, E.J.J. Tetrahedron Lett. 1995, 36, 5461.
8. a) Pri-Bar, I.; Buchman, O. J. Org. Chem. 1988, 53, 624.
9. b) Grushin, V.V.; Alper, H. J. Am. Chem. Soc. 1995, 117, 4305.
10. Cacchi, S.; Lupi, A. Tetrahedron Lett. 1992, 33, 3939.
11. 2 (254 mg, 1.14 mmol, 2 mol%), dppp (470 mg, 1.14 mmol, 2 mol%), and calcium formate(4.44 g, 34.2 mmol, 0.6 eq.) were added. The mixture was stirred at 80° C while kept under 1 atm CO. After 20h the reaction was complete as seen by disappearance of 4 by HPLC. The mixture was cooled to r.t., diluted with EtOAc(1600 mL) and washed with 1N HC1(2 × 600 mL). The organic layer was filtered through Celite and the filtrate rotary evaporated to ∼200 mL total volume at which point crystallization was observed. The mixture was allowed stirred at 0° C for 2h to complete crystallization. The solid was collected and dried in vacuo to give SB 209963 as an off-white solid. Yield = 16.72g(72%).