Metal salts induced improved α-hydroxylation of ketones for the preparation of the key chiral intermediate of azole antifungals

Tetrahedron Asymmetry

Volumn 8, Issue 18, 1997, Pages 3047-3050

  Gala, Dinesh ^a   DiBenedetto, Donald J ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2',4' DIFLUORO 2 HYDROXYPROPIOPHENONE; ANTIFUNGAL AGENT; PROPIOPHENONE DERIVATIVE; UNCLASSIFIED DRUG;

ARTICLE; CATALYSIS; CHIRALITY; DRUG SYNTHESIS; HYDROXYLATION; IN VITRO STUDY; PRIORITY JOURNAL; REACTION ANALYSIS; STEREOCHEMISTRY; TEMPERATURE;

EID: 0030924007     PISSN: 09574166     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0957-4166(97)00403-5     Document Type: Article

References (29)

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24. This contrast from the enolate trapping experiments with 3 (also shown for desfluoro-3, ref. 10b) where only the Z silyl (TMS or TBDMS) enolethers are formed.
25. See Table 1, p. 3496 of ref. 5.
26. A dry ice/highly flammable diethyl ether bath is typically the combination of choice to obtain a reaction temperature of -90°C to -95°C. Alternatively, liquid nitrogen containing baths may be used to obtain this temperature. On the other hand, a dry ice/acetone bath is a more common, less constraining/flammable laboratory technique to obtain approx. -78°C reaction temperature and hence the latter is more preferable.
27. 2. It is possible that in some cases the salts either consumed NaHMDS and/or decomposed the oxaziridine.
28. For instability of 2 see: Gala, D.; Puar, M. S.; Kugelman, M.; DiBenedetto, D. J. J. Pharm. Sci. 1992, 81, 1199. For high yields, maintain cold (0-10°C) temperature, inert atmosphere and neutral pH during the workup and storage of the product as indicated in ref. 3a.
29. The ees were determined by HPLC (Chiracel OB; 4-7% iPrOH/Hexane, 0.7 to 1.1 mL/min, UV 220nm).