Enzymatic resolution of (RS)-2-(1-aminoethyl)-3-chloro-5-(substituted) pyridines

Tetrahedron Asymmetry

Volumn 15, Issue 18, 2004, Pages 2797-2799

  Sigmund, Amy E ^a   DiCosimo, Robert ^a  

^a DUPONT COMPANY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ACETIC ACID ETHYL ESTER; PYRIDINE DERIVATIVE;

ACETYLATION; ANALYTIC METHOD; ARTICLE; CANDIDA ANTARCTICA; ENANTIOMER; ENANTIOSELECTIVITY; ENZYME ACTIVITY; ISOMERISM; NONHUMAN; PRIORITY JOURNAL; REACTION ANALYSIS; SUBSTITUTION REACTION;

EID: 4644319233     PISSN: 09574166     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.tetasy.2004.07.043     Document Type: Article

References (14)

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7. Lipases (ICR nos 101-117; ICR 110 = CALB lyo.) were obtained from BioCatalytics, Inc., Pasadena, CA
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10. 8,9 28 μL (0.20 mmol) of triethylamine, and 100 mg/mL of CALB in 2.0 mL of ethyl acetate were mixed at 30deg;C for 24 h. To the reaction mixture was then added 2.0 mL of 20 mM tetradecane (internal standard) in 1:1 acetonitrile/methanol, and the resulting mixture filtered (Gelman 0.2 μm GHP syringe filter) and analyzed by gas chromatography (GC). For HPLC analysis, a 0.100 mL aliqout of the filtrate was mixed with 0.400 mL of 150 mM N,N-dimethylbenzamide (HPLC internal standard) in 1:1 acetonitrile/methanol. Chiral GC analysis of (R)-2a-c and (S)-2a-c was performed using a GTA-40 column (Advanced Separation Technologies) at 160°C. No changes in relative amounts of (R)- and (S)-enantiomers of 2a were produced by the analysis, verified by analyzing a mixture of 9:1 (S)- and (R)-2a. Chiral HPLC analysis of (R)-2a-b and (S)-2a-b was also performed using UV detection at 280 nm on a (S,S)-Whelk-01 column (Regis, 25 cm ×- 4.6 mm id), using 30% isopropanol/70% hexanes (isocratic); ee was consistent with that measured by chiral GC analysis. Quantitation of (RS)-2a was performed on a DB-1701 GC column (J&W Scientific, 30 m, 0.53 mm OD, 1-μm film thickness). Chiral HPLC analysis of (R)-1a-c and (S)-1a-c was performed using UV detection at 280 nm on a Chiralcel OD-H column (Daicel, 25 cm ×- 4.6 mm id) at 30°C and a flow rate of 0.6 mL/min of 0.2% diethylamine in 10% 2-propanol/90% hexanes; N,N-dimethylbenzamide was used as internal standard
11. Resolution of (RS)-1a and (RS)-1b with (l)-(+)-tartaric acid [yielding (S)-1a and (S)-1b, respectively], and (d)-(+)-tartaric acid [yielding (R)-1b] produced standards used to confirm the enantiospecificity of CALB-catalyzed aminolysis reactions: H.E. Smith, L.J. Schaad, R.B. Banks, C.J. Wiant, and C.F. Jordan J. Am. Chem. Soc. 95 1973 811 818 The absolute stereochemistry for products 2a-c were inferred from the configuration of the corresponding amines, which were acetylated
12. C.-S. Chen, Y. Fujimoto, G. Girdaukas, and C.J. Sih J. Am. Chem. Soc. 104 1982 7294 7298
13. 2OBrCl (M+1) 276.9743, found 276.9733
14. A.E. Sigmund, K.C. McNulty, D. Nguyen, C.E. Silverman, P. Ma, J.A. Pesti, and R. DiCosimo Can. J. Chem. 80 2002 608 612