Improved stereoselectivity in the heterogeneous catalytic synthesis of enalapril obtained through multidimensional screening

Tetrahedron Letters

Volumn 40, Issue 5, 1999, Pages 831-834

  Huffman, Mark A ^a   Reider, Paul J ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ENALAPRIL;

AMINATION; ARTICLE; CATALYSIS; CHEMICAL ANALYSIS; CHEMICAL REACTION; DRUG SYNTHESIS; REDUCTION; STEREOCHEMISTRY;

EID: 0033613691     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(98)02590-8     Document Type: Article

References (14)

1. a) Sigman, M.S.; Jacobsen, E.N. J. Am. Chem. Soc. 1998, 120, 4901-4902.
2. b) Cole, B.M.; Shimizu, K.D.; Krueger, C.A.; Harrity, J.P.A.; Snapper, M.L., Hoveyda, A.H. Angew. Chem. Intl. Ed. Engl. 1996, 35, 1668-1671.
3. c) Burgess, K.; Lim, H.-J.; Porte, A.M., Sulikowski, G.A. Angew. Chem. Intl. Ed. Engl. 1996, 35, 220-222.
4. d) Gilbertson, S.R.; Wang, X. Tetrahedron Lett. 1996, 37, 6475-6478.
5. e) Liu, G.; Ellman, J.A. J. Org. Chem. 1995, 60, 7712-7713.
6. f) Menger, F.M.; Eliseev, A.V.; Migulin, V.A. J. Org. Chem. 1995, 60, 6666-6667.
7. g) Gennari, C.; Nestler, H.P.; Piarulli, U.; Salom, B. Liebigs Ann./Recueil 1997, 637-647.
8. For a novel approach to screening heterogeneous catalysts, see: Moates, F.C.; Somani, M.; Annamalai, J.; Richardson, J.T.; Luss, D.; Willson, R.C. Ind. Eng. Chem. Res. 1996, 35, 4801-4803.
9. Blacklock, T.J.; Shuman, R.F.; Butcher, J.W.; Shearin, W.E. Jr.; Budavari, J.; Grenda, V.J. J. Org.Chem. 1988, 53, 836-844.
10. The hydrogenation reactor consisted of a cylindrical glass vessel 9 cm in diameter, with a glass cap connected via an O-ring-sealed flange and clamp. A joint in the cap was connected to a hydrogen/nitrogen/vacuum manifold. Individual reaction mixtures were placed in 8 mL vials fitted with septum-containing screw caps. A short 18 gauge needle was placed through each cap to allow gasses to pass through while preventing cross-contamination by splashing. The vials were placed in a rack consisting of a circular teflon plate drilled with 18 wells to accommodate the vials. Magnetic stir bars in the vials allowed mixing with a strong magnetic stirrer placed under the reactor.
11. Representative screening procedure: Alanyl proline (1.395 g, 7.5 mmol) and powdered 3A sieves (2.88 g) were suspended in a mixture of absolute ethanol (11.25 mL) and acetic acid (3.75 mL). To the suspension was then added ethyl-2-oxo-4-phenylbutyrate (1.56 ml, 8.25 mmol). From the rapidly stirring suspension, 1.3 mL portions were removed by pipetter (with wide-bore tip) and transferred into 8 mL vials which had previously been charged with LiF (13 mg, 26 mg, 52 mg) or KF (29 mg, 58 mg, 116 mg). Some of the vials had also been previously charged with 10 mg of 5 % platinum on alumina; the remainder were charged with 100 mg of ethanol-wet Raney-Nickel after receiving the reagent slurry. The vials were placed in the glass pressure vessel (ref. 4). After vacuum/nitrogen purging, the mixtures were stirred under one atm hydrogen at ambient temperature for 21 h. Samples from each vial were diluted 1000X, filtered and assayed by HPLC using an autosampler.
12. Blaser, H.-U.; Jalett, H.-P.; Müller, M.; Studer, M. Catal. Today 1997, 37, 441-463.
13. Optimized reaction conditions: In a hydrogenation reactor, potassium fluoride (1.53 g, 26.3 mmol), alanyl proline (4.66 g, 25.0 mmol), powdered 3A sieves (9.6 g), and acetic acid (1.88 g, 31.3 mmol) are combined in 48 mL anhydrous ethanol. The mixture is inerted with nitrogen, and to it is added ethanol-wet Raney-Nickel (5.13 g). Ethyl-2-oxo-4-phenylbutyrate is added last (6.20 g, 27.5 mmol). After vacuum degassing, the mixture is stirred under one atm of hydrogen at 22 °C for 18 h. When reaction completion is confirmed by HPLC, the mixture is filtered through Solka Floc rinsing with ethanol. (Caution: Raney-Nickel must not be allowed to dry out.) Crystallization of the salt with maleic acid (ref. 3) gives 9.97 g, 81 %, vs. 76 % using the standard reaction conditions.
14. For a more extensive discussion of multidimensional reaction screening, see: Porte, A.M.; Reibenspies, J.; Burgess, K. J. Am. Chem. Soc. 1998, 120, 9180-9187.